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Flavonoids are ubiquitous compounds in nature and are found in many Chinese herbal medicines. Due to their biological activity, flavonoids show potential for decreasing insulin resistance (IR), thereby delaying the progression of diabetes and accompanying metabolic syndromes. This review focuses on the mechanisms of flavonoids decreasing IR: (1) the interaction between flavonoids and target proteins of the insulin signalling pathway; (2) bioactivities of flavonoids, such as anti-inflammatory, lipid-lowering and antioxidant. Meanwhile, we summarise the structural characteristics, structure activity relationships and biological activity of flavonoids, providing evidence for their potential in the treatment of IR. Here, we also analyse the potential and limitations of their therapeutic use. [ABSTRACT FROM AUTHOR]

The COVID-19 epidemic has been spreading around the world for nearly three years, and asymptomatic infections have exacerbated the spread of the epidemic. To analyse and evaluate the role of asymptomatic infections in the spread of the epidemic, we establish an improved COVID-19 infectious disease dynamics model. We fit the epidemic data in the four time periods corresponding to the selected 614G, Alpha, Delta and Omicron variants and obtain the proportion of asymptomatic persons among the infected persons gradually increased and with the increase of the detection ratio, the cumulative number of cases has dropped significantly, but the decline in the proportion of asymptomatic infections is not obvious. Therefore, in view of the hidden transmission of asymptomatic infections, the cooperation between various epidemic prevention and control policies is required to effectively curb the spread of the epidemic. [ABSTRACT FROM AUTHOR]

Our goal in this work was to investigate the possible role and mechanism of regulated in development and DNA damage response 1 (REDD1) in mediating high glucose (HG)-induced podocyte injury in vitro. Mouse podocytes were stimulated with HG to establish HG injury model. Protein expression was examined by Western blotting. Cell viability was measured by cell counting kit-8 assay. Cell apoptosis was assessed by annexin V‐FITC/propidium iodide and TUNEL apoptotic assays. Levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were quantified by commercial kits. Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were measured by ELISA. A marked increase in REDD1 expression was observed in podocytes stimulated with HG. Reduced REDD1 expression strikingly restrained HG-induced increases in apoptosis, oxidative stress, and inflammation response in cultured podocytes. Decreasing REDD1 expression enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) activation in HG-exposed podocytes via regulation of the AKT/glycogen synthase kinase-3 beta (GSK-3β) pathway. Inhibition of AKT or reactivation of GSK-3β prominently abolished Nrf2 activation induced by decreasing REDD1 expression. Pharmacological repression of Nrf2 markedly reversed the protective effects of decreasing REDD1 expression in HG-injured podocytes. Our data demonstrate that decreasing REDD1 expression protects cultured podocytes from HG-induced injuries by potentiating Nrf2 signaling through regulation of the AKT/GSK-3β pathway. Our work underscores the potential role of REDD1-mediated podocyte injury during the development of diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Objective: Mental illness is a growing public concern, particularly for persons in higher education. This research aims to distinguish mental health and stigma experiences between three academic communities: undergraduate students, graduate students, and faculty members. Methods: The researchers conducted semi-structured interviews with nineteen individuals who self-identified as a member of one or more of these groups. Findings and discussion: Participants reported experiencing a variety of mental health conditions (e.g., depression, anxiety, and post-traumatic stress), and described having diverse cognitive, affective, and behavioral responses to internally and externally derived stigma. The findings of this study also provide insights into the ways that academic communities observe and interpret on-campus communication about mental health, and participants offered impressions about ways to improve intervention and awareness messaging. Implications of the findings are discussed. [ABSTRACT FROM AUTHOR]

Promoting professional development of in-service language teachers is key to maintaining education quality. However, extant studies on test-based continuing professional development (CPD) for teachers do not emphasise primary school contexts in China, leading to difficulties in the professional development of this teacher group. Therefore, this paper reports the influences of CPD, based on the Teaching Knowledge Test (TKT) programme for in-service primary school English teachers in China, particularly concerning dynamic changes in their professional beliefs and self-efficacy due to participation in the programme. In this study, 42 English teachers were recruited from 15 primary schools to participate in the CPD programme. Through focus groups and teachers' journals, the findings showed that the teachers experienced complex transformations in their professional beliefs and self-efficacy, and revealed some influential factors of the change. This paper provides suggestions to optimise CPD programmes and facilitate long-term professional development for teachers. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) mainly occurs in pregnant women and is hereditary. Several genome-wide association studies (GWAS) on Caucasian samples have reported some gene loci that are associated with preeclampsia. However, these studies have not reached consistent conclusions. No previous GWAS has examined preeclampsia in the Chinese Han population. This study aimed to identify common genetic variations associated with preeclampsia in the Chinese Han population through two-stage case‒control studies. The discovery cohort included 92 patients with severe preeclampsia and 187 healthy controls. The validation cohort included 52 patients with preeclampsia and 104 controls. A genome-wide association study was performed to identify putative preeclampsia genes in the discovery cohort, with validation in the validation cohort. In the discovery cohort, GWAS demonstrated that 19 single-nucleotide polymorphisms (SNPs) were associated with preeclampsia (P < 10−5). The pathway analysis revealed that these 19 SNP representative genes were mainly enriched in the adenylyl cyclase-inhibiting G-protein coupled receptor signaling pathway. After validation in the validation cohort, rs13176432 and rs13210237 remained closely related to preeclampsia (P<0.05). In the combined data set, the frequency of the G allele in rs13176432 was significantly higher in cases with preeclampsia than in controls (P = 5 × 10−6). The frequency of the A allele in rs13210237 was higher in the preeclampsia group (P = 8 × 10−6). The rs13210237 representative genes include HSF2 and GJA1, while the rs13176432 representative gene is TRIM36. There were no differences in genotype distribution between the early-onset and late-onset preeclampsia groups (P > 0.05). Furthermore, rs13210237 and rs13176432 were related to preeclampsia in the adjusted regression model (P < 0.000). In this study of two independent cohorts, we found that rs13210237 and rs13176432 might be novel preeclampsia-susceptible genetic factors in the Han population in China. However, there was no association between the onset of preeclampsia and these genotypes. [ABSTRACT FROM AUTHOR]

As institutions of higher education continue to offer online instruction, educators and administrators of presentational speaking courses must adapt their classes for various modes of online delivery. One primary consideration for adapting a presentational speaking course to online delivery is how students will experience communication apprehension and/or public speaking anxiety in online communication contexts. The instructional communication field is rife with research about students' experiences with speech anxiety and communication apprehension. However, little work has explored how students' experiences may differ when the primary mode of course communication and course presentations is mediated through either synchronous or asynchronous modes of online communication. If these anxieties in face-to-face settings can deter students' academic and professional goals (Richmond et al., Communication apprehension, avoidance, and effectiveness [6th ed., Pearson, 2013]), researchers should investigate students' experiences in online courses. The current study begins to fill this gap. We analyze qualitative responses (N = 178) to an open-ended survey distributed to undergraduates in presentational speaking courses. Thematic analysis revealed the uniqueness of online communication apprehension and its similarities to face-to-face communication apprehension. Implications for administrators and instructors of presentational speaking courses are offered. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy is a conserved cellular process associated with tumorigenesis and aggressiveness, while mechanisms regulating expression of autophagic machinery genes in cancers still remain elusive. Herein, we identified E2F4 (E2F transcription factor 4) as a novel transcriptional activator of cytoprotective autophagy crucial for zinc homeostasis in cancer cells. Gain- and loss-of-function studies showed that E2F4 promoted autophagy in a cell cycle-dependent manner, resulting in facilitated degradation of MT (metallothionein) proteins, elevated distribution of Zn2+ within autophagosomes, decreased labile intracellular zinc ions, and increased growth, invasion, and metastasis of gastric cancer cells. Mechanistically, E2F4 directly regulated the transcription of ATG2A (autophagy related 2A) and ULK2 (unc-51 like autophagy activating kinase 2), leading to autophagic degradation of MT1E, MT1M, and MT1X, while USP2 (ubiquitin specific peptidase 2) stabilized E2F4 protein to induce its transactivation via physical interaction and deubiquitination in cancer cells. Rescue experiments revealed that USP2 harbored oncogenic properties via E2F4-facilitated autophagy and zinc homeostasis. Emetine, a small chemical inhibitor of autophagy, was able to block interaction between UPS2 and E2F4, increase labile intracellular zinc ions, and suppress tumorigenesis and aggressiveness. In clinical gastric cancer specimens, both USP2 and E2F4 were upregulated and associated with poor outcome of patients. These findings indicate that therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression. Abbreviations: 3-MA: 3-methyladenine; ANOVA: analysis of variance; ATG2A: autophagy related 2A; ATG5: autophagy related 5; ATP: adenosine triphosphate; BECN1: beclin 1; BiFC: bimolecular fluorescence complementation; CCND1: cyclin D1; CDK: cyclin dependent kinase; ChIP: chromatin immunoprecipitation; CHX: cycloheximide; Co-IP: co-immunoprecipitation; DAPI: 4',6-diamidino-2-phenylindole; E2F4: E2F transcription factor 4; eATP: extracellular adenosine triphosphate; EBSS: Earle's balanced salt solution; FP: first progression; FRET: fluorescence resonance energy transfer; FUCCI: fluorescent ubiquitination-based cell cycle indicator; GFP: green fluorescent protein; GST: glutathione S-transferase; HA: hemagglutinin; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MDM2: MDM2 proto-oncogene; MKI67/Ki-67: marker of proliferation Ki-67; MT: metallothionein; MT1E: metallothionein 1E; MT1M: metallothionein 1M; MT1X: metallothionein 1X; MTT: 3-(4,5-dimethyltriazol-2-yl)-2,5-diphenyl tetrazolium bromide; OS: overall survival; PECAM1/CD31: platelet and endothelial cell adhesion molecule 1; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; qPCR: quantitative PCR; RFP: red fluorescent protein; SQSTM1/p62: sequestosome 1; UBXN1: UBX domain protein 1; Ub: ubiquitin; ULK2: unc-51 like autophagy activating kinase 2; USP14: ubiquitin specific peptidase 14; USP2: ubiquitin specific peptidase 2; USP5: ubiquitin specific peptidase 5; USP7: ubiquitin specific peptidase 7; ZnCl2: zinc chloride. [ABSTRACT FROM AUTHOR]

Delineation of the groundwater's potential zones is a growing phenomenon worldwide due to the high demand for fresh groundwater. Therefore, the identification of potential groundwater zones is an important tool for groundwater occurrence, protection, and management purposes. More specifically, in arid and semi-arid regions, groundwater is one of the most important natural resources as it supplies water during the drought period. The present research study focused on the delineation of potential groundwater zones in Saveh City, the northern part of the Markazi Province in Iran. The groundwater potential mapping was prepared using hybrid deep learning and machine learning algorithm of the boosted tree (BT), artificial neural network (ANN), deep learning neural network (DLNN), deep learning tree (DLT), and deep boosting (DB). This study was carried out by using fourteen groundwater potential conditioning factors and 349 each for springs and non-springs points. The performance of each model was validated through statistical analysis of sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and receiver operating characteristic (ROC)-area under curve (AUC) analysis. The validation result showed that the success rate of AUC is very good for the DB model (0.87–0.99) and other models are also good i.e. BT (0.81–0.90), ANN (0.77–0.82), DLNN (0.84–0.86), and DLT (0.83–0.91). Among the several factors used in this study altitude, rainfall, distance to fault and soil types are the more important conditioning factors for groundwater potential modeling. Finally, all the models in this study had high efficiency in groundwater potential mapping, but it is recommended to use the Deep Boost model due to the better results in future studies. The result of this work will be useful to planners for optimal use and future planning of groundwater. [ABSTRACT FROM AUTHOR]

Piping erosion is one of the water erosions that cause significant changes in the landscape, leading to environmental degradation. To prevent losses resulting from tube growth and enable sustainable development, developing high-precision predictive algorithms for piping erosion is essential. Boosting is a classic algorithm that has been successfully applied to diverse computer vision tasks. Therefore, this work investigated the predictive performance of the Boosted Linear Model (BLM), Boosted Regression Tree (BRT), Boosted Generalized Linear Model (Boost GLM), and Deep Boosting models for piping erosion susceptibility mapping in Zarandieh Watershed located in the Markazi province of Iran. A piping inventory map including 152 piping erosion locations was prepared for algorithm training and testing. 18 initial predisposing factors (altitude, slope, plan curvature, profile curvature, distance from river, drainage density, distance from road, rainfall, land use, soil type, bulk density, CEC, pH, clay, silt, sand, topographical position index (TPI), topographic wetness index (TWI)) was derived from multiple remote sensing (RS) sources to determine the piping erosion prone areas. The most significant predisposing factors were selected using multi-collinearity analysis which indicates linear correlations between predisposing factors. Finally, the results were evaluated for Sensitivity, Specificity, Positive predictive values (PPV) and Negative predictive value (NPV), and Receiver Operation characteristic (ROC) curve. The best Sensitivity (0.80), Specificity (0.84), PPV (0.85), NPV (0.79), and ROC (0.93), were obtained by Deep Boosting model. The results of the piping erosion susceptibility study in agricultural land use showed that 41% of agricultural lands are very sensitive to piping erosion. This outcome will enable natural resource managers and local planners to assess and take effective decisions to minimize damages to agricultural land use by accurately identifying the most vulnerable areas. Hence, this research proved Deep Boosting model's ability for piping erosion susceptibility mapping in comparison to other popular methods such as BLM, BRT, and Boost GLM. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a type of progressive dementia caused by degeneration of the nervous system. A single target drug usually does not work well. Therefore, multi-target drugs are designed and developed so that one drug can specifically bind to multiple targets to ensure clinical effectiveness and reduce toxicity. We synthesised a series of 2-arylbenzofuran derivatives and evaluated their in vitro activities. 2-Arylbenzofuran compounds have good dual cholinesterase inhibitory activity and β-secretase inhibitory activity. The IC50 value of compound 20 against acetylcholinesterase inhibition (0.086 ± 0.01 µmol·L−1) is similar to donepezil (0.085 ± 0.01 µmol·L−1) and is better than baicalein (0.404 ± 0.04 µmol·L−1). And most of the compounds have good BACE1 inhibitory activity, of which 3 compounds (8, 19 and 20) show better activity than baicalein (0.087 ± 0.03 µmol·L−1). According to experimental results, 2-arylbenzofuran compounds provide an idea for drug design to develop prevention and treatment for AD. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis is a chronic systemic disease characterised by an unknown aetiology of inflammatory synovitis. A large number of studies have shown that synoviocytes show tumour-like dysplasia in the pathological process of RA, and the changes in the expression of related cytokines are closely related to the pathogenesis of RA. In this thesis, a series of novel 3-(4-aminophenyl) coumarins containing different substituents were synthesised to find new coumarin anti-inflammatory drugs for the treatment of rheumatoid arthritis. The results of preliminary activity screening showed that compound 5e had the strongest inhibitory activity on the proliferation of fibroid synovial cells, and it also had inhibitory effect on RA-related cytokines IL-1, IL-6, and TNF-α. The preliminary mechanism study showed that compound 5e could inhibit the activation of NF-κB and MAPKs signal pathway. The anti-inflammatory activity of compound 5ein vivo was further determined in the rat joint inflammation model. [ABSTRACT FROM AUTHOR]

Multi-target drugs can better address the cascade of events involved in oxidative stress and the reduction in cholinergic transmission that occur in Alzheimer's disease than cholinesterase inhibitors alone. We synthesised a series of 3-arylbenzofuranone derivatives and evaluated their antioxidant activity, cholinesterase inhibitory activity, and monoamine oxidase inhibitory activity. 3-Arylbenzofuranone compounds exhibit good antioxidant activity as well as selective acetylcholinesterase inhibitory activity. The IC50 value of anti-acetylcholinesterase inhibition of Compound 20 (0.089 ± 0.01 μM) is similar to the positive drug donepezil (0.059 ± 0.003 μM). According to the experimental results, Compounds 7, 13 show a certain effect in the in vitro evaluation performed and have the potential as drug candidates for the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) remains recalcitrant to effective treatment due to tumor relapse and acquired resistance. Cancer stem cells (CSCs) are believed to be one mechanism for relapse and resistance and are consequently considered promising drug targets. We report that chetomin, an active component of Chaetomium globosum, blocks heat shock protein 90/hypoxia-inducible factor 1 alpha (Hsp90/HIF1α) pathway activity. Chetomin also attenuated sphere-forming, a stem cell-like characteristic, of NSCLC CSCs (at ~ nM range) and the proliferation of non-CSCs NSCLC cultures and chemoresistant sublines (at ~ μM range). At these concentrations, chetomin exerted a marginal influence on noncancerous cells originating from several organs. Chetomin markedly decreased in vivo tumor formation in a spontaneous KrasLA1 lung cancer model, flank xenograft models, and a tumor propagation flank implanted model at doses that did not produce an observable toxicity to the animals. Chetomin blocked Hsp90/HIF1α pathway activity via inhibiting the Hsp90-HIF1α binding interaction without affecting Hsp90 or Hsp70 protein levels. This study advocates chetomin as a Hsp90/HIF1α pathway inhibitor and a potent, nontoxic NSCLC CSC-targeting molecule. [ABSTRACT FROM AUTHOR]

Alzheimer's disease, a neurodegenerative illness, has the extremely complex pathogenesis. Accumulating evidence indicates there is a close relationship between several enzymes and Alzheimer's disease. Various substituted 3-arylcoumarin derivatives were synthesised, and their in vitro activity, including cholinesterase inhibitory activity, monoamine oxidase inhibitory activity, and antioxidant activity were investigated. Most of the compounds exhibited high activity; therefore 3-arylcoumarin compounds have the potential as drug candidates for the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

A variety of substituted 3-arylcoumarin derivatives were synthesised through microwave radiation heating. The method has characteristics of environmental friendliness, economy, simple separation, and purification process, less by-products and high reaction yield. Those 3-arylcoumarin derivatives were screened for antioxidant, α-glucosidase inhibitory and advanced glycation end-products (AGEs) formation inhibitory. Most compounds exhibited significant antioxidant and AGEs formation inhibitory activities. Anti-diabetic activity studies showed that compounds 11 and 17 were equipotent to the standard drug glibenclamide in vivo. According to the experimental results, the target compound 35 can be used as a lead compound for the development of new anti-diabetic drugs. The whole experiment showed that anti-diabetic activity is prevalent in 3-arylcoumarins, which added a new natural skeleton to the development of anti-diabetic active drugs. [ABSTRACT FROM AUTHOR]

Subgroup analysis, as the key component of personalized medicine development, has attracted a lot of interest in recent years. While a number of exploratory subgroup searching approaches have been proposed, informative evaluation criteria and scenario-based systematic comparison of these methods are still underdeveloped topics. In this article, we propose two evaluation criteria in connection with traditional type I error and power concepts, and another criterion to directly assess recovery performance of the underlying treatment effect structure. Extensive simulation studies are carried out to investigate empirical performance of a variety of tree-based exploratory subgroup methods under the proposed criteria. A real data application is also included to illustrate the necessity and importance of method evaluation. [ABSTRACT FROM AUTHOR]

In this study, we introduced novel hybrid of evidence believe function (EBF) with logistic regression (EBF-LR) and logistic model tree (EBF-LMT) for landslide susceptibility modelling. Fourteen conditioning factors were selected, including slope aspect, elevation, slope angle, profile curvature, plan curvature, topographic wetness index (TWI), stream sediment transport index (STI), stream power index (SPI), distance to rivers, distance to faults, distance to roads, lithology, normalized difference vegetation index (NDVI), and land use. The importance of factors was assessed using correlation attribute evaluation method. Finally, the performance of three models was evaluated using the area under the curve (AUC). The validation process indicated that the EBF-LMT model acquired the highest AUC for the training (84.7%) and validation (76.5%) datasets, followed by EBF-LR and EBF models. Our result also confirmed that combination of a decision tree-logistic regression-based algorithm with a bivariate statistical model lead to enhance the prediction power of individual landslide models. [ABSTRACT FROM AUTHOR]

The work is focused on the design of drugs that prevent and treat diabetes and its complications. A novel class of stilbene derivatives were prepared by coupling NO donors of alkyl nitrate and were fully characterised by NMR and other techniques. These compounds were tested in vitro activity, including α-glucosidase inhibitory activity, aldose reductase (AR) inhibitory activity and advanced glycation end products (AGEs) formation inhibitory activity. A class of modified compounds could play a significant effect for treatment of diabetic complications. Target compounds 3e and 7c offered a potential drug design concept for the development of therapeutic or preventive agents for diabetes and its complications. [ABSTRACT FROM AUTHOR]

1.Glucuronidation of amines has been shown to exhibit large species differences, where the activity is typically more pronounced in human than in many preclinical species such as rat, mouse, dog and monkey. The purpose of this work was to characterize the in vitro glucuronidation of GNE-924, a potent pan-PIM inhibitor, to form M1 using liver microsomes (LM) and intestinal microsomes (IM). 2.M1 formation kinetics varied highly across species and between liver and intestinal microsomes. In LM incubations, rat exhibited the highest rate of M1 formation (CLint,app) at 140 ± 10 µL/min/mg protein, which was approximately 30-fold higher than human. In IM incubations, mouse exhibited the highest CLint,app at 484 ± 40 µL/min/mg protein, which was >1000-fold higher than human. In addition, CLint,app in LM was markedly higher than IM in human and monkey. In contrast, CLint,app in IM was markedly higher than LM in dog and mouse. 3.Reaction phenotyping indicated that UGT1A1, UGT1A3, UGT1A9, UGT2B4 and the intestine-specific UGT1A10 contributed to the formation of M1. 4.This is one of the first reports showing that N-glucuronidation activity is significantly greater in multiple preclinical species than in humans, and suggests that extensive intestinal N-glucuronidation may limit the oral exposure of GNE-924. [ABSTRACT FROM AUTHOR]

Objectives: Acute lymphoblastic leukemia (ALL) is the most common cancer before the age of 15 years, seriously endangering the health of children. The main treatment for Childhood ALL was pharmacotherapy. But these drugs have many side effects and some of them could develop drug resistance quickly. Mometasone furoate (MF) is an efficient glucocorticoid for topical treatment of inflammation on the skin, lung and nose. Methods: In this study, we investigated whether the MF had effects on ALL cells proliferation and migration. Results: The CCK-8 proliferation test showed that the cell viability was the lowest at 25 nM MF treatment and the increased OD value was time-dependent. In transwell assay, the number of CCRF-CEM cells was reduced in MF treated group. We found the expression of anti-apoptotic protein bcl-2 decreased the expression of pro-apoptotic protein caspase3 and bax increased in CCRF-CEM cell line treated with MF. The expression of p-AKT, p-mTOR, p70S6 K, vascular endothelial growth factor and CyclinD1 were decreased in MF treated group. Conclusion: This study reveals that MF can inhibit proliferation and invasion/migration and induce apoptosis in Childhood ALL cells, which may be regulated by Phosphatidylinositol 3- kinase signaling pathway. These results suggest MF may be a potential new drug target for clinical ALL treatment. [ABSTRACT FROM AUTHOR]

In network simulation, higher simulation accuracy generally leads to significantly increased computational overhead. To mitigate this issue, we present a new network simulation method for the focusing topology area (NESFOTA). The idea is to partition the topology into two parts that are complementary to each other, namely the focusing topology area and the non-focusing topology area. The focusing topology area is of interest to the simulation users and it is simulated using the traditional packet-level models to attain satisfactory accuracy. On the other hand, the non-focusing topology area is simulated with a higher level of abstraction to decrease the computational overhead. In particular, a method is proposed for the non-focusing topology area simulation, and theoretical analysis shows that it degrades marginally the simulation accuracy of focusing topology area. Compared to the traditional method, the NESFOTA method reduces the computational overhead by about 10 times at most while achieving nearly the same simulation accuracy of focusing topology area. [ABSTRACT FROM AUTHOR]

The new structure of two-oriented corrugated plate is developed in an oil–water separator. The surface of the corrugated plate is modified so that one side is provided with a hydrophobic property and the other side is provided with a hydrophilic property. The effect of feed flow rate and composition on the separation efficiency of the separator is analyzed by experiments. A three-dimensional model of the separator is established for simulation by using the fluent software. The separation effect is characterized by the maximum concentration and thickness of the two constituents. The simulation results are in good agreement with the experimental results. The feed composition and feed flow rate can be worked together in the coalescence process. Both in the experiment and in the simulation, the concentration of the outlet of this polynode separator can reach more than 99% in the treatment of oil-bearing rate from 30% to 60% and inlet flow rate at 800 L/h∼2000 L/h, which confirms the high separation efficiency of the device structure. At the same time, it also can be concluded that the lower oil phase concentration is suitable for larger inlet flow, while higher oil phase concentration is more applicable for lower flow rate in the appropriate range. [ABSTRACT FROM PUBLISHER]

PSMB1 (proteasome subunit beta type 1) is a core component of the 20S proteasome, and based on its structure, it might have a crucial function in the transcription of certain genes. Rheb (Ras homolog enriched in brain) is a Ras-like small GTPase that acts as an upstream positive regulator of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. We cloned and characterizedPSMB1(KY310590.1) to determine its function in cell cycle progression and proliferation of goat fetal fibroblasts (GFbs). Further, by yeast two-hybrid screen and coimmunoprecipitation, we conformed that PSMB1 interacts directly with Rheb. An siRNA was designed and expressed targetingPSMB1mRNA in GFbs and inducing cell cycle arrest.Rheboverexpression in GFbs significantly increased the number of S phase cells and growth efficiency compared with control cells. These data indicate thatPSMB1andRhebhave important functions in the cell cycle and proliferation of GFbs, indicating that their interaction governs many processes in GFbs. Abbreviations:GFbs: Cashmere goat fetal fibroblasts; mTOR: The mechanistic target of rapamycin; PSMB1: proteasome subunit beta type 1; Rheb: Ras homolog enriched in brain [ABSTRACT FROM AUTHOR]

Rare earth elements (REEs) contamination to the surrounding soil has increased the concerns of health risk to the local residents. Soil washing was first attempted in our study to remediate REEs-contaminated cropland soil using nitric acid, citric acid, and ethylene diamine tetraacetic acid (EDTA) for soil decontamination and possible recovery of REEs. The extraction time, washing agent concentration, and pH value of the washing solution were optimized. The sequential extraction analysis proposed by Tessier was adopted to study the speciation changes of the REEs before and after soil washing. The extract containing citric acid was dried to obtain solid for the X-ray fluorescence (XRF) analysis. The results revealed that the optimal extraction time was 72 h, and the REEs extraction efficiency increased as the agent concentration increased from 0.01 to 0.1 mol/L. EDTA was efficient to extract REEs over a wide range of pH values, while citric acid was around pH 6.0. Under optimized conditions, the average extraction efficiencies of the major REEs in the contaminated soil were 70.96%, 64.38%, and 62.12% by EDTA, nitric acid, and citric acid, respectively. The sequential extraction analyses revealed that most soil-bounded REEs were mobilized or extracted except for those in the residual fraction. Under a comprehensive consideration of the extraction efficiency and the environmental impact, citric acid was recommended as the most suitable agent for extraction of the REEs from the contaminated cropland soils. The XRF analysis revealed that Mn, Al, Si, Pb, Fe, and REEs were the major elements in the extract indicating a possibile recovery of the REEs. [ABSTRACT FROM AUTHOR]

In the present paper, general analytical formulas for calculating the Young's modulus and Poisson's ratio of single-walled carbon nanocones (SWCNCs) at finite temperatures are derived based on the proposed temperature-related multiscale quasi-continuum (QC) model. To this end, a temperature-related higher-order Cauchy-Born (THCB) rule is employed to establish the hyper-elastic constitutive model of SWCNCs. With use of the proposed approach, the influences of the temperature, apex angle, rotation angle of cutting lines and top end radius on the Young's moduli and Poisson's ratios of SWCNCs are investigated systematically. [ABSTRACT FROM PUBLISHER]

This study aimed to investigate the therapeutic effects of aspirin (ASA) and its potential mechanisms of action in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. PAH was induced in a rat model by a single intraperitoneal (IP) injection of MCT. Saline was injected in a control group. Two weeks following MCT injection, right ventricular systolic pressure (RVSP) and systolic blood pressure (SBP) were measured in six rats from each group to confirm establishment of a PAH model. The remaining MCT-treated rats were randomly allocated to receive IP injection of saline, ASA, or ERK1/2 inhibitor PD98059. Four weeks following treatment, RVSP was measured and all rats were sacrificed for histological study. There was no significant difference in SBP in any group two weeks following MCT administration. Nonetheless RVSP was significantly increased in the MCT group compared with the control group. At 6 weeks, ASA treatment remarkably attenuated MCT-induced increased RVSP, RV hypertrophy, and pulmonary artery remodeling compared with the MCT group. The density of pulmonary capillaries in ASA-treated rats was also dramatically increased. Treatment with ASA significantly inhibited the increased p-ERK1/2 and restored the impaired endothelial nitric oxide synthase (eNOS) in MCT-treated rats. This study demonstrated that ASA distinctively attenuates MCT-induced PAH by inhibition of the ERK1/2 signaling pathway. [ABSTRACT FROM PUBLISHER]

This study reports further characterization of the defence mechanism of an EMS-induced mutant (MNR220) that displays enhanced resistance to leaf rust, stem rust, stripe rust and powdery mildew diseases. The broad-spectrum resistance of the mutant was characterized by a microscopy study and additional race screenings of two rust pathogens. The mutant displayed less disease severity in response to all the races tested, when compared with the wild-type. The microscopy study of the pathogenesis of a leaf rust race PBJJG on the mutant revealed that the resistance was first evident at the pre-haustorial stage; formation of haustoria was significantly delayed or inhibited in the mutant compared with the wild-type. The mutant displayed microscopic level of cell death even in the absence of any pathogens. These findings suggest that MNR220 mediates a spontaneous cell death that delays the infection process by delaying haustoria formation of the pathogen. [ABSTRACT FROM PUBLISHER]

The brightness non-uniformity caused by vignetting effects, viewing, and illumination angels in remote sensing images reduces the interpretation precision. A multi-resolution variational Retinex scheme is proposed in this paper to efficiently correct the non-uniform brightness in airborne remote sensing images. This variational Retinex model is non-linear, constrained by the grey-world assumption and the total variation regularization. A Gaussian image pyramid is used to construct the multi-resolution scheme. The multi-resolution scheme reduces the calculation burden and raises the calculation efficiency. The fast split Bregman (SB) iteration method is employed to optimize the proposed non-linear model in each level of the multi-resolution scheme. This decomposes the complicated model into several simple sub-problems and greatly improves the calculation efficiency. The multi-resolution scheme embedded with the SB iteration method was applied to both synthetic and real remote sensing images. The experimental results show that the brightness non-uniformity can be corrected, and the spectral information can be effectively restored. Moreover, the calculation efficiency is raised by about 60–110 times, compared to the traditional single-resolution solving method. [ABSTRACT FROM AUTHOR]

1. Modern high-throughput small molecule drug discovery requires rapid screening of the pharmacokinetic parameters of multiple candidate molecules in parallel. The mouse is often used for such screening, as are solvent-based intravenous formulations. Despite this, the intravenous toxicity of many commonly used solvents is unknown. The purpose of this investigation is to establish recommended no-observed-effect level (NOEL) and maximum tolerated dose (MTD) for several commonly used intravenous solvents in the CD-1 mouse. 2. The acute tolerability of polyethylene glycol 400, N-methylpyrrolidone, dimethyl sulfoxide, ethanol, dimethylacetamide and propylene glycol was established, along with combinations of polyethylene glycol 400 and/or ethanol and DMSO. Based on these data, an acute NOEL and recommended MTD is reported for each solvent or solvent combination. 3. These data can guide the use of these solvents to support single-dose intravenous pharmacokinetic studies in mice. By establishing a defined dose tolerability range for the most commonly used intravenous solvents, undue pain and distress in animals can be avoided while maximizing the generation of critical pharmacokinetic data for project teams. [ABSTRACT FROM AUTHOR]

This article discusses subgroup identification, the goal of which is to determine the heterogeneity of treatment effects across subpopulations. Searching for differences among subgroups is challenging because it is inherently a multiple testing problem with the complication that test statistics for subgroups are typically highly dependent, making simple multiplicity corrections such as the Bonferroni correction too conservative. In this article, a Bayesian approach to identify subgroup effects is proposed, with a scheme for assigning prior probabilities to possible subgroup effects that accounts for multiplicity and yet allows for (preexperimental) preference to specific subgroups. The analysis utilizes a new Bayesian model selection methodology and, as a by-product, produces individual probabilities of treatment effect that could be of use in personalized medicine. The analysis is illustrated on an example involving subgroup analysis of biomarker effects on treatments. [ABSTRACT FROM AUTHOR]

Benzophenone group was introduced into the gel system in order to fabricate a new ALS2organogel which was photo-responsive. In the gel state with mixed solvent of acetone and water (5%), helical fibres were formed. The light control on the morphological change from fibres to core–shell spheres was followed by transmission electron microscope, which supplied a new paradigm for the morphology control triggered by stimulus. Moreover, the gel could serve as light absorbent without being mixed with polymer. [ABSTRACT FROM AUTHOR]

The radiation energy loss in a novel polysilicon chemical vapor deposition (CVD) reactor was simulated. The S2S radiation model was adopted. The simulated results demonstrate that enlarging the reactor capacity from 12 rods to 27 rods can: reduce the energy loss by 20.8%; by increasing the inner shield temperature from 373 to 773 K, the energy saving is 9.6%; if the polysilicon growth rate is increased from 5 to 20 μm · min−1, the radiation energy consumption can be reduced by 75%; and changing the emissivity of the inner shield from 0.2 to 0.1 decreases the energy loss by 38.3%. [ABSTRACT FROM AUTHOR]

Pure and vanadium doped NaTaO3 nanoparticles were synthesized by hydrothermal conditions. From XRD studies, both pure as well as vanadium doped NaTaO3 are found to show pure orthorhombic phase of tatanlate. STEM studies show the formation of cube shape particles in all the samples with a particle size about 70 nm. UV-vis diffuse reflectance spectra clearly indicates the red-shift in the series of vanadium doped NaTaO3 catalysts, resulting in a decrease in the band gap of NaTaO3 caused by substitution of V5+ ions at Ta5+ site with an increase of vanadium doping concentration in NaTaO3. The results reveal that Vanadium doped NaTaO3 show good photocatalytic performance under visible light and RhodamineB (RB) degradation is improved with Vanadium doping. The photocatalytic mechanism was discussed by density functional theory. V5+ ions substitution of Ta5+ ions results in an intermediate band (IB) below the bottom of the conduction band (CB), which is mainly attributed to the state of V 3d. Meanwhile the broadening of valence band is formed due to the hybridization between the V 3d and O 2p states. Both these factors increase the transient behavior of the photogenerated charge carriers and inhibit the recombination of e–h+ pairs, showing enhanced activities over the entire visible region. [ABSTRACT FROM AUTHOR]

The electrophilic fluorination of 4-chloropyrrolo[2,3-d]pyrimidine (1) was studied culminating a 59% conversion of compound 1 to 4-chloro-5-fluoropyrrolo[2,3-d]-pyrimidine (2) using Selectfluor. This transformation proceeded via the 4-chloro-5,6-dihydro-5-fluoro-6-hydroxypyrrolo[2,3-d]pyrimidine (3) in a 9:1 trans:cis ratio. The trans isomer of compound 3 was studied by &sup1]H NMR and [sup19]F NMR, and the 5-H tautomer (4) was observed as another intermediate. A modified Vorbruggen procedure of compound 2 and tetra-O-acetylribose gave 4-chloro-5-fluoro-7-(2,3,5,-tri-O-benzoyl-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine (6) in a 65% yield. Treatment of compound 6 with ammonia (l) in dioxane gave 5-fluorotubercidin (7). No antibacterial activity was observed. An MTT assay (Promega) against Huh-7 liver cells, normal mouse spleen cells stimulated with Con A (a T-cell mitogen), and normal mouse spleen stimulated with LPS (a B-cell mitogen) showed no significant toxicity. Increased activity of 7 over tubercidin was observed against L-1210 cells and toxicity in fibroblast cells was reduced. [ABSTRACT FROM AUTHOR]

AbstractWheat stripe rust disease caused by Puccinia striiformis f. sp. tritici (Pst) seriously affects wheat yield. We studied the fungal infection process and host response between wheat ‘AvS’ and its near-isogenic line ‘AvS+Yr10’, which formed compatible and incompatible interactions, respectively, when challenged with Pst race CYR32. The difference in reactive oxygen species (ROS) accumulation between the compatible and incompatible interactions was analyzed by measuring the hydrogen peroxide (H2O2) concentration and observing H2O2 production. Hydrogen peroxide concentrations, H2O2 accumulation areas, necrotic areas and expression of several resistance-related genes in the AvS+Yr10/CYR32 interaction were higher than those in the AvS/CYR32 interaction during the entire infection process. Pst growth was effectively inhibited in the AvS+Yr10 all-stage resistant wheat line. Thus, ROS accumulation is crucial in wheat defence against pathogens. [ABSTRACT FROM AUTHOR]