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Celecoxib is a specific cyclooxygenase-2 inhibitor with poor solubility and low bioavailability. A solid selfmicroemulsifying drug delivery system of celecoxib was therefore developed to improve in vitro drug solubility and in vivo absorption. Solubility testing, compatibility testing and pseudo-ternary phase diagrams were employed in the design. Morphological observation, droplet size and in vitro release were used to characterize the formulation. The optimized celecoxib-liquid self-microemulsifying drug delivery system was determined as 10 % of celecoxib, 25 % of medium chain triglycerides, 56.25 % of emulsifier and 18.75 % of Transcutol HP. 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay was used to investigate the cytoxicity of active pharmaceutical ingredients, blank self-microemulsion and celecoxib liquid self-microemulsifying drug delivery system on Caco-2 cells. Celecoxib solid self-microemulsifying drug delivery system was prepared with Neusilin-US2 as a solid adsorbent and characterized using scanning electron microscopy, X-ray, Fourier-transform infrared spectroscopy, differential scanning calorimetry and in vitro release. Celecoxib liquid self-microemulsifying drug delivery system had a clear and transparent light-yellow appearance with average particle size of about 22.68 nm, zeta potential of -31.92 mv, and polydisperse coefficient of 0.141. 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide results showed that the formulations virtually had no cytotoxic effect on the cells. The results also showed that celecoxib existed in an amorphous state in celecoxib-solid self-microemulsifying drug delivery system, and the celecoxib-liquid self-microemulsifying drug delivery system and celecoxib-solid-self-microemulsifying drug delivery system had a dissolution degree of more than 90 % in different media with good stability. The pharmacokinetic studies showed that the area under curve of the liquid self-microemulsifying drug delivery system and self-microemulsifying drug delivery system increased by 6.59 and 6.37 folds, respectively, compared with celecoxib suspension. The findings showed that the developed solid self-microemulsion formulations improved the bioavailability of the drug with no cytotoxicity, hence the formulation can serve as a promising carrier for the oral delivery of celecoxib. [ABSTRACT FROM AUTHOR]

Arctigenin (ARG) has potent antifatigue activity, but its clinical application has been restricted for its poor water solubility. In this study, seven ARG derivatives containing different amino acids coupled via an ethoxy linker were synthesized, and tested for their solubility, as well as activities to improve exercise performance in mice. All of the derivatives showed improved solubility compared to that of ARG. Derivative Z-A-6 exhibited the highest activity, showing that the mice ran a 4.88-fold greater distance in the running wheel test and swam a 2.86-fold greater time in the swimming test than those in the blank control group. Z-A-6 treatment increased the plasma superoxide dismutase and catalase concentrations as well as reduced lactic acid and blood urea nitrogen accumulation during exercise. Z-A-6 treatment enhanced the phosphorylation of adenosine monophosphate-activated protein kinase, and no acute toxicity was observed. The results will contribute to the development of potential antifatigue agents. [ABSTRACT FROM AUTHOR]

To fulfil the high precision requirements of the manoeuvre imaging mode of an agile satellite and solve the shortcomings of existing methods, a segmented attitude planning method based on the Pseudospectral method is proposed. First, a state equation was built by integrating the attitude constraint, time window and other restrictions. Furthermore, to guarantee the accuracy and stability of objects, a segmented strategy of an attitude trajectory approaching the imaging target using a constant angular velocity was proposed. The segmented time, three-axis position and velocity were also determined. Second, taking the global performance into account, the first section of the attitude trajectory was planned by the Legendre Pseudospectral method in order to acquire the optimal state variables and control variables. The second section of the attitude trajectory was then obtained by the constant angular velocity planning method. Next, in order to track the planning trajectory efficiently, a PD controller was designed that was suitable for a segmented planning method. High precision control parameters were obtained by the optimized method. Finally, numerical simulation results show that the proposed segmented attitude planning method successfully meets the high precision requirements of the manoeuvre imaging mode, and the feasibility and effectiveness of this method is verified. [ABSTRACT FROM AUTHOR]

B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E is the most common kinase-activating mutation and is associated with poor prognosis in melanoma. However, the clinical significance of kinase-impairing mutations remains unclear. The present study aimed to analyze kinase-impairing mutations in BRAF codons 594 and 596 in non-Caucasian patients with melanoma and to investigate their possible clinical significance. To detect hotspot mutations, exon 15 of the BRAF gene was amplified using polymerase chain reaction in samples from 1,554 patients with melanoma. Among these patients, a total of 912 valid follow-up data were obtained. These patients were divided into three groups according to their BRAF activation status: BRAF wild-type (n=752), BRAF V600E (n=147); and BRAF D594/G596 (n=13). Then the correlation between BRAF activation status, and the clinicopathological features and overall survival (OS) of the patients were analyzed. The prevalence of BRAF mutations in non-Caucasian patients with melanoma was 24.3% (377/1554). Three patients carried two mutations simultaneously. The overall mutation frequencies of kinase-activating mutations, kinase-impairing mutations, and mutations with unknown effects were 93.4 (355/380), 3.4 (13/380), and 3.2% (12/380), respectively. BRAF V600E was identified to be associated with a poor prognosis. Patients with BRAF mutations in codons 594 and 596 had a longer OS time compared with those with a BRAF V600E mutation [median OS, 45 vs. 25 months; HR, 0.45 (95% confidence interval, 0.31-0.97); P=0.043]. To the best of our knowledge, this is the first study to examine a large number of samples from non-Caucasian patients with melanoma and report the characteristics of BRAF mutations according to mutant kinase activity. Melanoma arising from a mutation in BRAF codon 594 or 596 can be differentiated from BRAF V600E-induced melanoma, and mutations in these codons may be good prognostic factors for melanoma. The results of the present study are thus of significance for the development of accurate personalized medicine to treat melanoma. [ABSTRACT FROM AUTHOR]

Purpose: To prepare ranitidine hydrochloride (RH) sustained-release suspension aimed at improving its safety, effectiveness and convenience of administration. Methods: The RH resinate suspension was prepared using bath method, with a cation- exchange resin as carrier. To obtain an ideal sustained release effect, RH resinates were coated with Eudragit®RS100 using the surface coating method, followed by optimization through a single-factor experiment and response surface analysis. The optimized RH suspension was characterized using accelerated stability test. Moreover, it was pharmacokinetically evaluated in vivo. Results: The optimized RH resin microcapsules showed relative mean deviation between the predicted and measured release values that was < 10 %, (p < 0.05) and demonstrated good reproducibility. Accelerated stability test results showed that the optimized RH suspension exhibited good stability over a period of 6 months (F > 0.9; drug content: 97 – 100 %, drug release: f2 > 50; drug leakage < 0.5 %), with good redispersibility. Results from pharmacokinetics showed that values of Tmax for RH sustainedrelease suspension and RH common tablet were 4.00 and 2.5 h, respectively (p < 0.05), while the corresponding Cmax values were 2545.78 and 3245.97 ng/mL, respectively (p < 0.05). Results of analysis of AUC0-24 showed that they were equivalent in terms of AUC0-24 (p < 0.05) and bioavailability of 101.05%. Conclusion: The optimized ranitidine hydrochloride (RH) sustained-release suspension has been successfully prepared using ion-exchange resin as a carrier and Eudragit® RS100 as a coating material. [ABSTRACT FROM AUTHOR]

Telomerase reverse transcriptase (TERT) copy number gain is frequently observed in Asian melanoma patients. Here, we explored the correlation between TERT copy number and the effect of telomerase inhibitors in melanoma. A total of 78 melanoma cases were enrolled in the study. The TERT copy number was examined by QuantiGene Plex DNA assay. The sensitivity to telomerase inhibitors was evaluated in cell lines and patient-derived xenograft (PDX) models with or without TERT copy number gain. Among the 78 patients, 33.3% showed TERT copy number gain, and the incidence of this gain in acral melanoma (61.5%) was higher than that in other melanoma subtypes (P=0.02). The telomerase inhibitors 6-thio-2'-deoxyguanosine (6-Thio-dG) and epigallocatechin-3-gallate (EGCG) inhibited cell viability and repressed tumor growth in PDX models with TERT copy number gain. TERT copy number gain is frequently observed in Chinese patients with melanoma. Targeting telomerase may benefit melanoma patients with TERT copy number gain. [ABSTRACT FROM AUTHOR]

Dysregulated lipid metabolism in liver is an important hallmark of non-alcoholic fatty liver disease (NAFLD), which may be modulated by dietary polyphenols or microRNAs (miRNAs). However, the underlying epigenetic regulatory mechanism of polyphenols remain unclear. The current study aimed to address how miRNA mediates hepatic lipid metabolic control of curcumin, a polyphenolic food supplement. The results showed that 24 h treatment with 5-20 µM curcumin prevented free fatty acid-induced lipid accumulation by around 10-50% in HepG2 cells, which was attenuated by pre-transfection with 40 nM miR-22-3p mimic for 48 h. In consequence, transfection with 40 nM miR-22-3p inhibitor for 48 h significantly reduced lipid accumulation by around 10%. And, 48 h overexpression of miR-22-3p targeting cardiolipin synthase 1 (CRLS1) gene, which encodes a mitochondrial phospholipid synthase, showed a similar regulatory effect. Thus, miR-22-3p and CRLS1 showed opposite effects in modulating lipid metabolism, which probably involved mitochondrial control. In summary, this study demonstrated that curcumin improved hepatic lipid metabolism via targeting the miR-22-3p/CRLS1 pathway. Identification of the epigenetic regulatory mechanism underlying lipid metabolism may thereby facilitate alleviation of metabolic disorders by natural polyphenols. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the use and applications of Internet cloud technology to construct a network management model for statin therapy in Alzheimer's disease in Hainan Province. Method: Randomized controlled trials (RCTs) investigating the prevention and treatment of Alzheimer's disease (AD) with statins were employed in this study. Computerized searches were conducted using PubMed, EM-BASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), WANFANG Data, and Curriculum-Based Measurement (CBM) retrieval systems, with a retrieval timeframe of April 2012. After literature screening, data extraction, and quality evaluation, Meta-analysis was performed using Review Manager 5.1.0 software. Results: A total of 827 publications were obtained, and 3 RCTs were included after the full texts were studied. While there was no significant advantage of statin use at 3 and 6 months after intervention, the study group exhibited higher Mini-Mental State Examination (MMSE) scores than the control group one year later (p < 0.05). Also, statin use did not have a significant effect on Activities of Daily Living (ADL) scores one year after intervention (p < 0.05). The occurrence of adverse reactions in the two groups was not statistically significant (p > 0.05). Conclusion: The use of Internet cloud technology for building an Alzheimer's disease network management system simplifies the process of Alzheimer's disease diagnosis and treatment, and reduces the cost of Alzheimer's disease services. [ABSTRACT FROM AUTHOR]

The Lanchang River is the upper stream of the Mekong River, which was one the most important communication gallery between the Yunnan Province and Southeast Asia region. Due to the intensive erosion of the Lanchang River, the landscape change is very rapid. However, the human activity and adaptation to the environmental changes in this region is still unknown. In this paper, Optically Stimulated Luminescence (OSL) and radiocarbon (14C) dating techniques were applied to determine the ages of fluvial landforms around the Jicha archaeological site, Middle reach of the Lanchang River since the Last Glacial Maximum. Combining these dating results with archaeological evidence, the relation between fluvial landscape change and human adaptation was discussed. The results showed that the two terraces (T1 and T2) of the Lanchang River are fill-cut terraces, and that these were formed after ~0.7-1.5 ka and 20-40 ka, respectively. With the downcutting of the Lanchang River, the floodplain facies on T1 being transformed into fossil soils, the latter being hostile to the planting of rice. The abandonment of the Jicha archaeological site might therefore be related to the downcutting of the Lanchang River. [ABSTRACT FROM AUTHOR]

Background: Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) is a unique subtype with poor prognosis, its response to systemic therapy is not fully understood, we evaluated the benefit of systemic therapy in these patients. Patients and Methods: Between May 2006 and December 2019, patients diagnosed with Xp11.2 tRCC from Peking university cancer hospital were collected. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Results: Metastatic Xp11.2 tRCC was found in 45 patients. The median PFS and median OS was 7.4 months (4.5-8.8) and 17.9 months (12.4-24.4), respectively. First-line treatment mainly included sunitinib (n = 14), sorafenib (n = 15), axitinib (n = 6), and pazopanib (n = 5), and the median PFS of these regimens were 7.4 months, 5.4 months, 9.4 months, 8.9 months, respectively. Two patients who received Vascular endothelial growth factor receptor - tyrosine kinase inhibitor (VEGFR-TKI) plus immune checkpoint inhibitor (ICI) as first line therapy had a PFS of more than 16.6 months and more than 25.6 months, respectively. Twenty-four patients received subsequent therapies, which included VEGFR-TKI/ICI, VEGFR-TKI and mTOR inhibitor. The ORR and median PFS was 33% and 7.1 months, 7.7% and 4.3 months, 0% and 2.1 months for these treatments, respectively. The estimated median OS was 17.3 months (95% CI, 11.2 to not reached) in patients with TKI/ICI treatment and 11.0 months (95% CI, 6.1 to not reached) without TKI/ICI treatment in subsequent therapies (P = .04). Patients with serous cavity effusion or IMDC poor risk groups had significantly shorter median PFS and median OS. Conclusion: Metastatic Xp11.2 tRCC is an aggressive disease. VEGFR-TKI agents appeared to demonstrate some efficacy, VEGFR-TKI/ICI combination might be a useful tool for the treatment of metastatic Xp11.2 tRCC. [ABSTRACT FROM AUTHOR]

[Display omitted] • VOF-DEM model was proved to be suitable for the coupled calculation of liquid and solid phases in jig separation. • Gas cycle in fluid-particle systems affected the pulsation, looseness, and separation of particles. • Reasonable gas working cycle was obtained for jig separation of clean coal and middling coal. Flexible air chamber jig is a new type of coal sorting and processing equipment with broad application prospects. The separation of coal particles in the jig mainly depended on the gas working cycle, liquid level height and particles looseness. This paper discusses the separation of clean coal and middling coal in this jig with simulation and experimental methods. Numerical simulation of jigger separation process was realized, and the effects of inlet, expansion and exhaust proportion on the water movement and particle separation were investigated based on the liquid level height, bed looseness and percentage of particles. It was verified by the water level detection experiments. The results showed that the model was accurate and the experimental results were consistent with the simulation. The maximum discrepancy between the water levels in the experiment and the simulation was less than 5%, confirming the accuracy of the VOF-DEM (Volume of Fluid-Discrete Element Method) model. The liquid level was significantly affected by the gas working cycles, while the bed looseness was mainly affected by the intake proportion. Appropriate intake and exhaust proportions increased the proportion of particles with different densities. A reasonable gas working period proportion for jigging separation: intake 24%, expansion 27%, and exhaust 24%. In this condition, the proportions of Zone 1′s clean coal and Zone 2′s medium coal is 81.16% and 94.18%, respectively. [ABSTRACT FROM AUTHOR]

Background: Coexistence of enhancer of zeste homolog 2 (EZH2) and BRAF gene aberrations has been described in many cancer types. In this study, we aim to explore the coexistence status of BRAF V600E mutation and the copy number variation of EZH2 and explore the potential of this combination as a therapeutic target.Methods: A total of 138 cases of melanoma samples harboring BRAF V600E mutation were included, and EZH2 copy numbers were examined by QuantiGenePlex DNA Assays. Clinical pathological distinction between patient groups with or without EZH2 amplification (hereafter referred to as EZH2 gain) was statistically analyzed. The sensitivity of melanoma cell lines and patient-derived xenograft (PDX) models containing BRAF V600E mutation with or without EZH2 gain to vemurafenib (BRAF inhibitor), GSK2816126 (EZH2 inhibitor) and a combination of both agents was evaluated.Results: In our cohort, the coexistence rate of BRAF V600E mutation and EZH2 gain was up to 29.0%, and significant differences in overall survival and disease-free survival were found between no EZH2 copy number gain and gain groups (P = 0.038, P = 0.030), gain and high EZH2 copy number gain groups (P = 0.006, P = 0.010). Combination with BRAF and EZH2 inhibition showed better inhibitory efficacy in melanoma prevention compared with vemurafenib monotherapy. More importantly, this improved therapeutic effect was observed especially in melanoma cell lines and PDX models containing concurrently BRAF V600E mutation and EZH2 gain.Conclusions: Coexistence of BRAF V600E mutation and EZH2 gain is rather prevalent in melanoma. Our findings provided evidence for the feasibility of combination therapy with EZH2 and BRAF inhibitors in melanoma with concurrent BRAF V600E mutation and EZH2 gain. [ABSTRACT FROM AUTHOR]

The red-emitting phosphor LaMgAl11O19:Sm3+, Eu3+ was prepared by solid-state reaction at 1600 °C for 4 h. The phase formation, luminescence properties, and energy transfer from Sm3+ to Eu3+ were studied. With the addition of 5 mol % Sm3+ as the sensitizer, the excitation wavelength of LaMgAl11O19:Eu3+ phosphor was extended from 464 to 403 nm, and the emission intensity under the excitation at 403 nm was also enhanced. The host material LaMgAl11O19 could contain the high doping content of Eu3+ (20 mol %) without concentration quenching. This energy transfer from Sm3+ to Eu3+ was confirmed by the decay times of energy donor Sm3+. The mechanism of energy transfer (Sm3+ → Eu3+) was proved to be quadrupole-quadrupole interaction. Under the 403 nm excitation at 150 °C, the emission intensities of the characteristic peaks of Sm3+ and Eu3+ in LaMgAl11O19:0.05Sm3+, 0.2Eu3+ phosphor were decreased to 65% and 56% of the initial intensities at room temperature, and the relatively high activation energy proved that this phosphor had a good thermal stability. The CIE coordinate was calculated to be (x = 0.601, y = 0.390). The LaMgAl11O19:0.05Sm3+, 0.2Eu3+ phosphor is a candidate for copper phthalocyanine-based solar cells and white light-emitting diodes. [ABSTRACT FROM AUTHOR]

Solid particle erosion-wear experiments on as-prepared mullite-SiC composite refractories by nitriding reactive sintering were performed at elevated temperatures, using sharp black SiC abrasive particles at an impact speed of 50 m/s and the impact angle of 90° in the air atmosphere. The effects of silicon powder addition and erosion temperature on the erosion-wear resistance of mullite-SiC composite refractories were studied. The test results reveal that Si powders caused nitriding reaction to form ß-sialon whiskers in the matrix of mullite-SiC composite refractories. The erosion-wear resistance of mullite-SiC composite refractories was improved with the increase of silicon powder addition and erosion temperature, and the minimum volume erosion rate was under the condition of 12% silicon added and a temperature of 1400°C. The major erosion-wear mechanisms of mullite-SiC composite refractories were brittle erosion at the erosion temperature from room temperature to 1000°C and then plastic deformation from 1200°C to 1400°C. [ABSTRACT FROM AUTHOR]

Optimal design of large induction motor is a process that involves electrical and mechanical skills as well as thermal and fluid dynamic skills. For recent machine layouts, one cannot rely on standard analysis methods. In multiphysics simulations which are done by weak coupling finite-element method, rotation boundary values on interface between air gap and rotor cannot be applied directly for fluiddynamical analysis. A novel multi-component fluid method is proposed to deal with the influence of rotor rotation upon the air convection. This paper investigates a 3-D multi-physics simulation used in simulation of temperature distribution in air-cooled induction motor. The temperature rise in motor is due to Joule's losses in stator windings and the induced eddy current in squirrel cages, and heat dissipation by air convection and solid conduction. The Joule's losses calculated by 3-D eddy-current field analysis are used as the input for the thermal field analysis, which deeply depends on accurate air fluid field analysis. Through the coupled-field calculation, we proposed a new ventilation structure of a 15-phase motor to improve the cooling performance. [ABSTRACT FROM AUTHOR]

• Plant invasion potentially alters ecosystem carbon (C) and nitrogen (N) cycles. However, the overall direction and magnitude of such alterations are poorly quantified. • Here, 94 experimental studies were synthesized, using a meta-analysis approach, to quantify the changes of 20 variables associated with C and N cycles, including their pools, fluxes, and other related parameters in response to plant invasion. • Pool variables showed significant changes in invaded ecosystems relative to native ecosystems, ranging from a 5% increase in root carbon stock to a 133% increase in shoot C stock. Flux variables, such as above-ground net primary production and litter decomposition, increased by 50–120% in invaded ecosystems, compared with native ones. Plant N concentration, soil and concentrations were 40, 30 and 17% higher in invaded than in native ecosystems, respectively. Increases in plant production and soil N availability indicate that there was positive feedback between plant invasion and C and N cycles in invaded ecosystems. • Invasions by woody and N-fixing plants tended to have greater impacts on C and N cycles than those by herbaceous and nonN-fixing plants, respectively. The responses to plant invasion are not different among forests, grasslands, and wetlands. All of these changes suggest that plant invasion profoundly influences ecosystem processes. [ABSTRACT FROM AUTHOR]

Whether plant invasion increases ecosystem carbon (C) stocks is controversial largely due to the lack of knowledge about differences in ecophysiological properties between invasive and native species. We conducted a field experiment in which we measured ecophysiological properties to explore the response of the ecosystem C stocks to the invasion of Spartina alterniflora ( Spartina) in wetlands dominated by native Scirpus mariqueter ( Scirpus) and Phragmites australis ( Phragmites) in the Yangtze Estuary, China. We measured growing season length, leaf area index (LAI), net photosynthetic rate (Pn), root biomass, net primary production (NPP), litter quality and litter decomposition, plant and soil C and nitrogen (N) stocks in ecosystems dominated by the three species. Our results showed that Spartina had a longer growing season, higher LAI, higher Pn, and greater root biomass than Scirpus and Phragmites. Net primary production (NPP) was 2.16 kg C m−2 y−1 in Spartina ecosystems, which was, on average, 1.44 and 0.47 kg C m−2 y−1 greater than that in Scirpus and Phragmites ecosystems, respectively. The litter decomposition rate, particularly the belowground decomposition rate, was lower for Spartina than Scirpus and Phragmites due to the lower litter quality of Spartina. The ecosystem C stock (20.94 kg m−2) for Spartina was greater than that for Scirpus (17.07 kg m−2), Phragmites (19.51 kg m−2) and the mudflats (15.12 kg m−2). Additionally, Spartina ecosystems had a significantly greater N stock (698.8 g m−2) than Scirpus (597.1 g m−2), Phragmites ecosystems (578.2 g m−2) and the mudflats (375.1 g m−2). Our results suggest that Spartina invasion altered ecophysiological processes, resulted in changes in NPP and litter decomposition, and ultimately led to enhanced ecosystem C and N stocks in the invaded ecosystems in comparison to the ecosystems with native species. [ABSTRACT FROM AUTHOR]