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Reflux hypersensitivity (RH) is a subtype of gastroesophageal reflux disease. The Rome IV criteria separated RH from the original nonerosive reflux disease subgroup and classified it as a new functional oesophageal disease. Recently, the pathogenesis of RH has become the focus of research. According to the latest research reports, upregulation of acid-sensitive receptors, distribution of calcitonin gene-related peptide-positive nerve fibres, and psychiatric comorbidity have key roles in the pathogenesis of RH. This work reviews the latest findings regarding RH mechanisms. [ABSTRACT FROM AUTHOR]

Background: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. Methods: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. Results: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. Conclusions: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms. [ABSTRACT FROM AUTHOR]

In polymer physics, the concept of entanglement refers to the topological constraints between long polymer chains that are closely packed together. Both theory and experimentation suggest that entanglement has a significant influence on the mechanical properties of polymers. This indicates its promise for materials design across various applications. However, understanding the relationship between entanglement and mechanical properties is complex, especially due to challenges related to length scale constraints and the difficulties of direct experimental observation. This research delves into how the polymer network structure changes when deformed. We specifically examine the relationship between entanglement, crosslinked networks, and their roles in stretching both entangled and unentangled polymer systems. For unentangled polymers, our findings underscore the pivotal role of crosslinking bond strength in determining the system's overall strength and resistance to deformation. As for entangled polymers, entanglement plays a pivotal role in load bearing during the initial stretching stage, preserving the integrity of the polymer network. As the stretching continues and entanglement diminishes, the responsibility for bearing the load increasingly shifts to the crosslinking network, signifying a critical change in the system's behavior. We noted a linear correlation between the increase in entanglement and the rise in tensile stress during the initial stretching stage. Conversely, the destruction of the network correlates with a decrease in tensile stress in the later stage. The findings provide vital insights into the complex dynamics between entanglement and crosslinking in the stretching processes of polymer networks, offering valuable guidance for future manipulation and design of polymer materials to achieve desired mechanical properties. [ABSTRACT FROM AUTHOR]

Objective: Excessive proliferation and migration of pulmonary arterial smooth muscle cell (PASMC) is a core event of pulmonary hypertension (PH). Regulators of G protein signaling 10 (RGS10) can regulate cellular proliferation and cardiopulmonary diseases. We demonstrate whether RGS10 also serves as a regulator of PH. Methods: PASMC was challenged by hypoxia to induce proliferation and migration. Adenovirus carrying Rgs10 gene (Ad-Rgs10) was used for external expression of Rgs10. Hypoxia/SU5416 or MCT was used to induce PH. Right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) were used to validate the establishment of PH model. Results: RGS10 was downregulated in hypoxia-challenged PASMC. Ad-Rgs10 significantly suppressed proliferation and migration of PASMC after hypoxia stimulus, while silencing RGS10 showed contrary effect. Mechanistically, we observed that phosphorylation of S6 and 4E-Binding Protein 1 (4EBP1), the main downstream effectors of mammalian target of rapamycin complex 1 (mTORC1) as well as phosphorylation of AKT, the canonical upstream of mTORC1 in hypoxia-induced PASMC were negatively modulated by RGS10. Both recovering mTORC1 activity and restoring AKT activity abolished these effects of RGS10 on PASMC. More importantly, AKT activation also abolished the inhibitory role of RGS10 in mTORC1 activity in hypoxia-challenged PASMC. Finally, we also observed that overexpression of RGS10 in vivo ameliorated pulmonary vascular wall thickening and reducing RVSP and RVHI in mouse PH model. Conclusion: Our findings reveal the modulatory role of RGS10 in PASMC and PH via AKT/mTORC1 axis. Therefore, targeting RGS10 may serve as a novel potent method for the prevention against PH.". [ABSTRACT FROM AUTHOR]

Enhanced understanding of turbulent flow structure in bends in natural rivers is essential for waterway regulation, navigation safety and environmental and ecological wellbeing. However, the flow structure in consecutive bends has so far remained poorly understood, especially when it is subject to the influence of tributary inflow. Here, the 3D flow structure in two consecutive bends, namely Qigongling (upstream bend) and Guanyinzhou (downstream bend), subject to the influence of tributary inflow from the Dongting Lake, in the middle Yangtze River, is numerically investigated. The RNG k-ϵ turbulence model is applied under the FLOW-3D software platform. The results show that: (1) the high-velocity zones shift from inner to outer banks in both consecutive bends. (2) No secondary current cells are spotted at the entrance of either bend. At the bend apex, multiple cells of secondary currents appear in Qigongling, but not in Guanyinzhou under certain discharges. (3) Recirculation vortices occur mainly on the inner bank (small-scale) in Qigongling, but on both the inner (small-scale) and outer (large-scale) banks in Guanyinzhou. (4) With increasing mainstem (tributary) discharge, the velocity and turbulent kinetic energy enlarge (reduce). However, a decrease of the secondary current strength in Qigongling and an increase in Guanyinzhou (all increase in both bends). [ABSTRACT FROM AUTHOR]

The sintered copper-based friction materials for high-speed train brake pads have a complex composition that should possess good physical, mechanical, and tribological properties in practical applications. For this article, four kinds of friction materials were prepared by powder metallurgy technology and the effects of iron powders on the microstructural and tribological properties of copper-based friction materials were characterized using a scanning electron microscope (SEM) and x-ray diffraction (XRD). The results showed that iron powder as an enhancing component could effectively change the friction and wear properties of the experimental materials. The copper-based friction materials containing hydroxy iron (1-5 lm) have a relatively higher coefficient of friction: The friction coefficient was significantly improved by 16.8% compared with reduced iron under a rotation speed of 4000 r/min. The friction coefficient of friction material containing wateratomized iron powder is relatively reliable with 3000-7000 r/min speed range. In a high-speed environment, the friction surface of material containing reduced iron or hydroxy iron (1-5 lm) mainly has cracks and brittle fractures, and the material containing hydroxy iron (10 lm) or wateratomized iron has an obvious layered structure and shows fatigue wear. [ABSTRACT FROM AUTHOR]

This article examines the current narrative of Chineseness in the context of higher education in Southeast Asia. We hypothesise that the concept of Chineseness at the macro-level has shifted beyond historical, ethnic, and cultural to include geopolitical, socio-political and economic considerations. At the meso level, we focus on unpacking Chineseness through the development of higher education institutions studying the case of Chinese established educational institutions in Malaysia, particularly in how these institutions articulate and portray their Chineseness in a multi-cultural higher education context. Having examined both macro and meso levels, the article discusses the importance and complexity of exploring Chineseness at the micro-level while also highlighting areas and gaps that have not allowed a more thorough understanding of Chineseness in the given context. Understanding this phenomenon allows us to explore the hypothesis of a shifting conceptualisation of Chineseness and thereby contribute to a more nuanced understanding of internationalisation and international students in higher education. [ABSTRACT FROM AUTHOR]

A biopsy of gastrocnemius muscle from a patient with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome was studied histologically in semithin sections stained by hematoxylin-and-eosin (H&E) and toluidine blue, and ultrathin sections by transmission electron microscopy (TEM). H&E stain demonstrated typical ragged-red fibers (RRFs) and affected fibers in fascicles. Toluidine-blue stain showed an irregular meshwork in the center of RRFs. TEM demonstrated damaged myofibrils and variations in mitochondrial structure in RRFs and affected fibers. Dense mitochondria were compacted with cristae and pleomorphic electron-dense inclusions. Lucent mitochondria included paracrystalline inclusions with a parking lot appearance. At high magnification, the paracrystalline inclusions were composed of plates that paralleled and connected with mitochondrial cristae. These observations indicated that electron-dense granular and paracrystalline inclusions resulted from cristal degeneration and overlapping in mitochondria in MELAS syndrome. [ABSTRACT FROM AUTHOR]

Background: Chronic urticaria (CU) is a prevalent dermatologic disease that negatively affects life, current therapies remain suboptimal. Hence, there is an urgent need to identify effective and safe treatment. Objective: Assess the efficacy and safety of compound glycyrrhizin (CG) combined with second-generation nonsedated antihistamine for the treatment of CU. Methods: Nine databases were queried to screen RCTs related. Two reviewers independently assessed the risk of bias using Cochrane Collaboration. Primary objective was the total efficiency rate, while secondary was rate of recurrence, adverse events, and cure. Statistical analyses using Review Manager 5.4 and Stata17. Results: Twenty-four RCTs were identified. Significant differences were noted in rate of total efficiency (n=2649, RR = 1.36, 95%CI:1.30–1.43, p<0.00001), cure (n=2649, RR = 1.54, 95%CI:1.42–1.66, p<0.00001) and recurrence (n=446, RR = 0.34, 95%CI:0.20–0.58, p<0.00001) between the combination of CG with second-generation non-sedated antihistamine and antihistamine monotherapy. Contrastingly, adverse events rate (n=2317, RR = 0.76, 95% CI:0.59–0.97, p=0.03) was comparable between the two groups. Our results indicated that CG combined with second-generation non-sedated antihistamine could significantly mitigate the symptoms in CU compared with antihistamine monotherapy. No serious adverse events were reported. Conclusions: CG combined with second-generation nonsedated antihistamine is effective for CU. Nevertheless, higher-quality studies are warranted to validate our results. [ABSTRACT FROM AUTHOR]

To examine the early outcomes, associated factors and predictive values of clinical outcomes of different tandospirone doses in patients with a generalized anxiety disorder (GAD). This was a posthoc analysis of "a randomized, controlled multicenter clinical trial of the efficacy and safety of different doses of tandospirone on GAD". A total of 274 patients with GAD were included and randomized into the high-dose (tandospirone 60 mg/d) and low-dose (tandospirone 30 mg/d) groups for a 6-week treatment. The Hamilton Anxiety (HAMA), Clinical Global Impression-Severity (CGI-S), Short-Form-12 (SF-12) scales were used for assessment. The trial was registered at clinical trail.gov (NCT01614041). (1) In the first week of treatment, 35.8% of patients in the high-dose group fulfilled the early onset criteria, which was significantly higher than 19.0% found in the low-dose group (p = 0.002). In the second week of treatment, 22.6% of patients in the high-dose group achieved an early response, versus 12.4% in the low-dose group, indicating a significant difference (p =.026). (2) Factors associated with early onset at week 1 included baseline HAMA total score (OR = 0.916, 95%CI 0.882–0.952), age (OR = 0.974, 95%CI 0.950–0.998), drug dose (30 mg vs. 60 mg; OR = 0.298, 95%CI 0.156–0.568) and SF-12 physiological total score (OR = 1.030, 95%CI 1.010–1.050). (3) Early onset was significantly associated with response rate (OR = 18.34, 95%CI 12.10–27.81), remarkable response rate (OR = 27.56, 95%CI 11.65–65.17) and recovery rate (OR = 11.85, 95%CI 4.98–28.18). Group (high dose group vs. low dose group) (χ2 = 8.535, p =.003) and baseline HAMA total score (χ2 = 70.840, p <.001) were independent predictors of onset time. The early outcomes of high-dose tandospirone in the treatment of GAD are better than those of the low-dose group. Patients with younger age at onset, milder anxiety symptoms and better physiological functions administered high-dose tandospirone showed rapid onset, great early outcomes, high recovery rate and good prognosis. Drug onset time had a good predictive effect on treatment outcome. [ABSTRACT FROM AUTHOR]

The dual-credit policy for auto manufacturers and the subsidy policy for charging infrastructure operators have become important policies to guide and promote the development of the automotive industry. However, few studies consider the impact of mixed policies on the market strategies of auto manufacturers and charging infrastructure operators considering consumer green preferences. To fill the gap, this article establishes optimization models to analyze and compare the effects of mixed policies on the decisionmaking of auto manufacturers and charging infrastructure operators under the cooperative and noncooperative modes considering consumer preference. The results reveal four main insights: (1) Two types of policies all have direct positive effects on the market diffusion of electric vehicles. Under the noncooperative mode, the dual-credit policy has no spillover effect. Under cooperative mode, two types of policies all have spillover effects. The dualcredit policy and charging infrastructure subsidy policy have positive superposition effects on the optimal number of charging piles, and the optimal demands for electric vehicles. (2) When the credit price is less than a certain threshold, there is a substitutive effect between the charging infrastructure subsidy policy and the dual-credit policy on promoting the market diffusion of electric vehicles. (3) There is a substitutive effect between high-level consumers' green preference and policies on promoting the market diffusion of electric vehicles. (4) Under the cooperative mode, the direct and spillover effects of policies are more than that are under the noncooperative mode. These insights demonstrate the effectiveness and limitations of policies and the importance of providing complementary policies for consumers. The government should encourage market cooperation between auto manufacturers and charging infrastructure operators, maintain a stable price level for credits, and introduce incentive policies for green consumption. [ABSTRACT FROM AUTHOR]

The circular RNAs (circRNAs) involved in competitive endogenous RNA (ceRNA) mechanism are critical modulators affecting pathogenesis of thyroid carcinoma (TC). The study's goal was to investigate the effects of circ 0003747 on the biological progression of papillary thyroid cancer (PTC). Normal thyroid cells Nthy-ori3-1 and TC derived cell lines were used in our study. Sanger sequencing and RNase R treatment were utilized for validating the circular structure of circ_0003747. In our work, circ_0003747 was found to be highly expressed in TC cells. Circ_0003747 knockdown reduced TC cell viability, proliferation, migration, and invasion while increasing cell apoptosis. Circ_0003747 targeted and negatively regulated miR-338-3p expression. Besides, miR-338-3p interacted with PLCD3 to repress its expression. Overexpression of miR-338-3p inhibited TC cell progression, and PLCD3 reversed these effects. Furthermore, PLCD3 overexpression reversed the effects of circ_0003747 knockdown on TC cells. Additionally, the knockdown of circ_0003747 remarkably suppressed tumour size and growth, restrained PLCD3 expression and promoted miR-338-3p expression in nude mice. In conclusion, circ_0003747 facilitated the biological progression of TC by modulating the miR-338-3p/PLCD3 axis, and it may be a new target for TC treatment. [ABSTRACT FROM AUTHOR]

Our previous work used two deformable pooling to get different feature regions for classification and regression to alleviate the spatial misalignment problem of the rotating ships based on a three-stage framework in remote sensing image. In this paper, we find that when the IoU threshold of the third stage is 0.55, the model gets the best average precision (AP). Besides, the deformable pooling is not suitable for negative samples and the effect of deformable pooling for positive samples will gradually weaken as the Intersection-over-Union (IoU) of the sample increase. We propose a complementary branch with IoU-based loss weight to enhance the training of the pooling feature. The more accurate the pooling feature, the more accurate the deformable pooling feature. Furthermore, we add an angle offset learning module to the regression task of the complementary branch to enhance the ability of pooling feature to learn angle offset. [ABSTRACT FROM AUTHOR]

Context: Pterostilbene (PTE), a common polyphenol compound, exerts an anti-inflammatory effect in many diseases, including acute lung injury (ALI). Objective: This study explores the potential mechanism of PTE pre-treatment against lipopolysaccharide (LPS)-induced ALI. Materials and methods: Sixty Sprague-Dawley rats were divided into control, ALI, 10 mg/kg PTE + LPS, 20 mg/kg PTE + LPS, and 40 mg/kg PTE + LPS groups. At 24 h before LPS instillation, PTE was administered orally. At 2 h before LPS instillation, PTE was again administered orally. After 24 h of LPS treatment, the rats were euthanized. The levels of inflammatory cells and inflammatory factors in the bronchoalveolar lavage fluid (BALF), the expression of nuclear receptor subfamily 4 group A member 1 (NR4A1), and the nuclear factor (NF)-κB pathway-related protein levels were detected. NR4A1 agonist was used to further investigate the mechanism of PTE pre-treatment. Results: After PTE pre-treatment, the LPS induced inflammation was controlled and the survival rate was increased to 100% from 70% after LPS treatment 24 h. For lung injury score, it decreased to 1.5 from 3.5 after treating 40 mg/kg PTE. Compared with the control group, the expression of NR4A1 in the ALI group was decreased by 20-40%. However, the 40 mg/kg PTE pre-treatment increased the NR4A1 expression by 20-40% in the lung tissue. The results obtained with pre-treatment NR4A1 agonist were similar to those obtained by pre-treatment 40 mg/kg PTE. Conclusions: PTE pre-treatment might represent an appropriate therapeutic target and strategy for preventing ALI induced by LPS. [ABSTRACT FROM AUTHOR]

Context: Atorvastatin (ATV) and QiShenYiQi pills (QSYQ), a Chinese patent medicine, are often co-prescribed to Chinese cardiovascular patients. The effects of QSYQ on the pharmacokinetics of ATV have not been studied. Objective: We investigated the influence of QSYQ on the pharmacokinetics of ATV and its metabolites upon oral or intravenous administration of ATV to rats. Materials and methods: Sprague-Dawley rats (n = 5/group) were pre-treated with oral QSYQ (675 mg/kg) or vehicle control for 7 days and then orally administrated ATV (10 mg/kg) or intravenously administrated ATV (2 mg/kg). Serum concentrations of ATV and metabolites were determined by ultra-high performance liquid chromatography tandem mass spectrometry. Expression of metabolic enzymes and transporters in jejunum and ileum were measured by quantitative real-time PCR and Western blot. Results: QSYQ resulted in an increase of AUC0-12 h of ATV from 226.67 ± 42.11 to 408.70 ± 161.75 ng/mL/h and of Cmax of ATV from 101.46 ± 26.18 to 198.00 ± 51.69 ng/mL and in an increased of para-hydroxy atorvastatin from 9.07 ± 6.20 to 23.10 ± 8.70 ng/mL in rats administered ATV orally. No change was observed in rats treated intravenously. The expression of multidrug resistance-associated protein 2 mRNA and protein decreased in ileum, and the mRNA of P-glycoprotein decreased in jejunum, though no change in protein expression was found. Discussion and conclusions: QSYQ increased bioavailability of ATV administered orally through inhibiting the expression of Mrp2 in ileum. Clinicians should pay close attention to potential drug-drug interactions between ATV and QSYQ. [ABSTRACT FROM AUTHOR]

Three new compounds, polygalapyrone A (1), tenuiside G (2) and polygalapyrrole A (3), together with two known compounds (4–5) were isolated by silica gel, ODS and preparative HPLC from the aerial part of Polygala tenuifolia. Their structures were elucidated by spectrum analysis and compared with findings from the literature. The anti-inflammatory effects of those compounds were investigated in vitro. [ABSTRACT FROM AUTHOR]

Background: To determine the relationship between gestational diabetes mellitus (GDM) and coagulation/fibrinolysis abnormality in antenatal Chinese women. Methods: Case control study: 50 women had GDM and 132 did not (the NGDM group) grouping by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Maternal plasma biochemistry and previous medical history were collected from perinatal health records. Antenatal coagulation/fibrinolysis activity (CFA) parameters were assessed using thromboelastography and routine CFA parameters, respectively. Univariate and multiple regression analyses were used to evaluate the associations between GDM and CFA parameters. Maternal age, platelet, ALT, ALP, urea nitrogen, and previous history of abortion were taken as the covariables. Results: The women with GDM were significantly older than those without GDM (30.3 vs. 28.6 years, p=.012). Compared with the NGDM group, the GDM group had a significantly higher prevalence of cesarean delivery (56.0 vs. 37.9%, p=.027) and higher values of fibrinogen (FIB; 4.7 vs. 4.3 g/L, p=.001), activated partial thromboplastin time (APTT; 30.9 vs. 29.5 s, p=.010). There were no significant differences in the prevalence of maternal thrombotic events or neonatal events. GDM was significantly associated with higher APTT (b =1.41 s, 95% CI: 0.29-2.53), higher FIB (b = 0.38 g/L, 95% CI: 0.14-0.61), and higher percentage reduction in clot lysis after 30 min (LY30; b=1.14%, 95% CI: 0.15-2.13) after adjustment for potential confounding factors. Conclusions: GDM is significantly associated with hypercoagulability and hyperfibrinolysis in these antenatal Chinese women. [ABSTRACT FROM AUTHOR]

One new lactone derivative helicascolide F (1), one new pyrrolidine derivative talaromydine (2), along with six known compounds (3–8) were isolated from the fungus Talaromyces assiutensis JTY2. The structure of the new compounds 1 and 2 was determined by 1D and 2D NMR as well as by HRESIMS. The inhibitory activity of all compounds against six phytopathogenic fungi and three cancer cell lines was evaluated. [ABSTRACT FROM AUTHOR]

To identify the nature of foam cells in atherosclerosis, carotid atherosclerotic plaques (CAPs) from six patients were studied. Hematoxylin-and-eosin, Congo Red and Oil Red O staining were used to study histopathologic alterations in CAPs. CD31, α-smooth-muscle actin (α-SMA), CD68, desmin and S100 were stained immunohistochemically. The ultrastructure of foam cells was analyzed by transmission electron microscopy (TEM). CAPs were shown to be composed of a fibrous cap covering a dome-shaped mass with a peripheral, circumferential fringe merging with a basal band which itself met the tunica media, the latter consisting of smooth-muscle cells (SMCs). The interior of the dome-shaped mass exhibited fibrosis, neovascularization, hemorrhage, necrosis and calcification. Lipid droplets identified by histological stains and TEM were found in the rounded epithelioid foam cells regarded as macrophages, as well as in spindled cells interpreted here as lipoleiomyocytes (lipid-containing SMCs), lipofibroblasts and lipomyofibroblasts; and all these cells were located in different regions of the CAPs. All of these lipid-laden cells were strongly positive for CD68 but negative for desmin. Foam cells were weakly positive for α-SMA, CD31 and S100. The results indicate that the light microscopically identifiable population of foam/lipid-laden cells hide a spectrum of diverse differentiation ranging from the expected macrophage phenotype to non-macrophage phenotypes. The origin of these diverse cell phenotypes in terms of multipotential mesenchymal precursors and the origin of the intracellular lipid are discussed. [ABSTRACT FROM AUTHOR]

Background: Transgender women of Color experience disproportionate rates of HIV, depression, and anxiety, and high rates of substance use, attempted suicide, and interpersonal verbal, physical, and sexual violence and assault. However, there are few interventions targeting transgender women of Color that address overlapping health and mental health challenges. Aims: There are two aims/research questions: (1) what are the elements of a transgendercentric model for delivering evidence based interventions and practices?, and (2) does Seeking Safety improve substance use and mental health outcomes for transgender women of Color?. Methods: We present a case study of the delivery process of Seeking Safety by Special Service for Groups/Asian Pacific AIDS Intervention Team (SSG/APAIT), and analyze baseline and three month post program participant data (n = 81). Results: The transgender-centric model of intervention delivery consisted of multiple steps, also integrating the structural disadvantages experienced by transgender women of Color. Comparing baseline and three months after completion showed significant decrease in reported alcohol use, depression, and severe anxiety. Discussion: Transgender-centric approaches may lead to programs that significantly improve co-occurring substance use and mental health for transgender women of Color. We recommend that organizations aiming to existing programs include feedback from members of the communities that the adapted programs aim to help, and in addition, train community members to deliver the programs. The statistical results indicate that Seeking Safety, a trauma-based program with a short program delivery timeline, may show longer term effects on substance use and mental health. We recommend that programs targeting substance use and mental health for transgender women of Color should be combined with services that address disadvantage (i.e., lack of access to housing, income/employment, health care). [ABSTRACT FROM AUTHOR]

The dilatancy equation plays a significant role in establishing an elastoplastic constitutive model for soils. The rockfills will show strain-softening or strain-hardening behaviour according to the testing confining pressure and/or initial void ratio. Therefore, a new dilatancy equation for rockfill materials incorporating strain hardening and strain softening was studied. A series of triaxial compression tests on rockfills were carried out to investigate the material constants and applicability of the proposed dilatancy equation (PDE). The material constants Mc, β, a and c of the PDE were found to be independent of the initial void ratio and confining pressure. At the dilatancy point and critical state, the observed dilatancy of soils is zero, while the PDE was proved to fully meet these conditions. In addition, the PDE can well depict the trends of the observed dilatancy behaviour during the whole shearing, even though the dilatancy behaviour from the peak point to the critical state is difficult to be simulated for many existing equations. By comparing with three widely used dilatancy equations, the simulated strain-volume curves by a constitutive model using the PDE are significantly acceptable, no matter whether the rockfill is strain hardening or strain softening. [ABSTRACT FROM AUTHOR]

The CHA2DS2-VASc score is a guideline-recommended stroke risk stratification scheme for patients with atrial fibrillation (AF). Accurately calculating the CHA2DS2-VASc score and recognizing the stroke risk in AF patients is the foundation of optimal anticoagulation therapy. This survey aims to obtain a comprehensive understanding of perceptions and knowledge gaps on CHA2DS2-VASc scores among Chinese medical professionals for future education programs. A cross-sectional survey was conducted among clinicians, including cardiologists, neurologists, emergency physicians (EPs), general practitioners (GPs) and clinical pharmacists (CPs) using a self-administered questionnaire on the Chinese mainland. The survey contained 21 questions in combination with single-choice questions, multiple-choice questions, and an open-ended question, which was distributed online via e-mail or social media. A total of 562 participants (40.9% cardiologists, 19.2% neurologists, 8.5% EPs, 10.3% GPs, and 21.0% CPs) completed the survey. Most respondents across all specialties reported skills requiring improvements in the CHA2DS2-VASc score. In general, cardiologists, neurologists, and CPs had a relatively better understanding than GPs and EPs about the application of CHA2DS2-VASc score. Considering 'H' and 'D' components, more than 90% of respondents chose the correct answer in single-choice questions, whereas the correctness rate declined concerning detailed scoring criteria. Regarding 'C,' 'A2,' 'S2,' and 'V' components, partly correct answers were commonly observed in most multiple-choice questions. The majority of cardiologists believed themselves to be very familiar or at least familiar with the score and its components, while around 70% of EPs and GPs felt relatively unfamiliar with the CHA2DS2-VASc score. Mobile apps, AF guidelines and notebooks/handbooks were popular referencing scoring tools for respondents. Chinese medical professionals, especially EPs and GPs, revealed a lack of knowledge and insufficient skills for CHA2DS2-VASc scores and their components. Improvements in the awareness of the CHA2DS2-VASc score and its detailed scoring criteria are urgently needed for Chinese medical professionals. Therefore, education programs concerning the introduction of stroke risk evaluation for AF patients and the development of referencing scoring tools are necessary. [ABSTRACT FROM AUTHOR]

To clarify the characteristics and origin of the cellular components in atherosclerosis, carotid atherosclerotic plaques (CAPs) of four patients were studied by light microscopy using hematoxylin-eosin, Congo red and alpha-smooth-muscle actin stains, and by transmission electron microscopy of different regions of CAPs. By light microscopy, CAPs were composed of 1) a fibrous cap; 2) an atherosclerotic core presenting focal fibrosis, neovascularization, hemorrhage, necrosis, chondrification and ossification; and 3) a basal band composed of a hyperplasic pseudo-media and affected tunica media. Ultrastructurally, the CAPs contained a diversity of cells including fibroblasts, myofibroblasts, osteochondrocytes, vascular smooth-muscle cells, foam cells and other myoid cells characterized by varied features of the above mentioned cells. The results indicated that CAPs were derived from a proliferation of multipotential mesenchymal stem cells, leading to the presence of degenerated foam cells and lipid-laden cells. [ABSTRACT FROM AUTHOR]

Background: Associations of dietary or supplementary intake of several unsaturated fatty acids and mortality have been widely studied but the results were still hitherto inconsistent or limited. It is still need to explore the effects of these fatty acids by using the objective biomarkers. Objective: We aimed to investigate the relevancy of several serum n-3 and n-6 fatty acids with all-cause and disease-specific mortality to confirm their health effects and effects on the associations between dietary quality and all-cause mortality. Methods: A total of 4132 people from NHANES 2003-2004 and 2011-2012 and the mortality information was confirmed from the NDI. CPH models adjusted for known risk factors were conducted to explore the associations between circulating n-3 and n-6 fatty acids and all-cause or CVD or cancer mortality under complex sampling. We further evaluated their effects on association between dietary quality and all-cause mortality. Results: A total of 437 deaths occurred during the mean follow-up of 83.34months, including 157 CVD death and 100 cancer death. Serum LA, ALA, EPA and DHA were associated with allcause mortality (HR in quintile5: LA:0.584, 95%CI: 0.387-0.882, Ptrend=0.011; ALA:0.626, 95%CI: 0.432-0.907, Ptrend=0.008; EPA:0.535, 95%CI: 0.375-0.764, Ptrend=0.001; DHA:0.669, 95%CI: 0.468-0.955, Ptrend=0.031). Additionally, serum EPA and ALA were respectively related to CVD and cancer mortality (Q5 HR: EPA:0.450, 95%CI: 0.23-0.854, Ptrend=0.009; ALA:0.387, 95%CI: 0.167-0.900, Ptrend=0.022). Serum AA, GLA, DGLA and SDA were not associated with any risk of mortality. The effect on all-cause mortality of the lower AHEI scores can be improved by adherence to a higher serum LA, EPA and DHA (in the lowest AHEI strata, LA in tertile3 compared to tertile1 HR:0.596, 95%CI: 0.366-0.970; EPA:0.660, 95%CI: 0.454-0.959; DHA:0.666, 95%CI; 0.444-1.000). Conclusions: Our results support the recent dietary recommendations to increase the intake of plant-derived and marine-derived n-6 and n-3 to improve the ability of primary and secondary prevention. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a pivotal cause of global women cancer death. Immunotherapy has become a promising means to cure breast cancer. As constitutes of immune microenvironment of breast cancer, macrophages exert complicated functions in the tumour development and treatment. This study aims to develop a prognostic macrophage marker genes signature (MMGS). Methods: Single cell RNA sequence data analysis was performed to identify macrophage marker genes in breast cancer. TCGA database was used to construct MMGS model as a training cohort, and GSE96058 dataset was used to validate the MMGS as a validation cohort. Results: Genes included in the MMGS model were: SERPINA1, CD74, STX11, ADAM9, CD24, NFKBIA, PGK1. MMGS risk score stratified by overall survival of patients divided them into highand low-risk groups. And MMGS risk score remained independent prognostic factor in multivariate analysis after adjusting for classical clinical factors in both training and validation cohorts. Besides, hormone receptors negative and human epidermal growth factor receptor 2 (HER2) positive patients had higher risk score. MMGS showed better distinguishing capability between high-risk and low-risk groups in hormone receptor positive and HER2 negative subgroup. Conclusion: MMGS provides a new understanding of immune cell marker genes in breast cancer prognosis and may offer reference for immunotherapy decision for breast cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of oral sitafloxacin versus levofloxacin in Chinese adults with acute uncomplicated urinary tract infection (UTI) or complicated UTI. Methods: In this randomized, active-controlled clinical trial, the patients with acute uncomplicated UTI were randomized to receive sitafloxacin 100-mg once-daily (qd) or levofloxacin 500- mg qd orally for 3-5 days. The patients with complicated UTI were randomized to receive sitafloxacin 100-mg twice daily or levofloxacin 500-mg qd orally for 10-14 days. The primary endpoint was the clinical efficacy at test-of-cure (TOC) visit. Results: At TOC visit, the clinical cure rate was 89.2% (58/65) in sitafloxacin group and 97.1% (68/70) in levofloxacin group for the patients with acute uncomplicated UTI corresponding to the bacterial eradication rate of 97.1% (34/35) and 97.6% (41/42) (all p>.05), respectively. For the patients with complicated UTI, the clinical cure rate was 81.8% (27/33) in sitafloxacin group and 76.9% (20/26) in levofloxacin group corresponding to the bacterial eradication rate of 93.3% (14/15) and 63.6% (7/11) (all p>.05), respectively. Sitafloxacin and levofloxacin showed similar incidence of drug-related adverse events. Conclusions: Oral sitafloxacin is as effective and safe as levofloxacin in treating acute uncomplicated and complicated UTI. [ABSTRACT FROM AUTHOR]

Gastric cancer is one of the leading causes of cancer-related death worldwide with a poor prognosis. Gastric cancer is usually treated with surgery and chemotherapy, accompanied by a high rate of metastasis and recurrence. In this paper, R8 (RRRRRRRR) modified vinorelbine plus schisandrin B liposomes had been successfully constructed for treating gastric cancer. In the liposomes, R8 was used to enhance the intracellular uptake, schisandrin B was incorporated into liposomes for inhibiting tumor cells metastasis, and vinorelbine was encapsulated into liposomes as antitumor drugs. Studies were performed on BGC-823 cells in vitro and were verified in the BGC-823 cell xenografts nude mice in vivo. Results in vitro demonstrated that the targeting liposomes could induce BGC-823 cells apoptosis, inhibit the metastasis of tumor cells, and increase targeting effects to tumor cells. Meanwhile, action mechanism studies showed that the targeting liposomes could down-regulate VEGF, VE-Cad, HIF-1a, PI3K, MMP-2, and FAK to inhibit tumor metastasis. In vivo results exhibited that the targeting liposomes displayed an obvious antitumor efficacy by accumulating selectively in tumor site and induce tumor cell apoptosis. Hence, R8 modified vinorelbine plus schisandrin B liposomes might provide a safe and efficient therapy strategy for gastric cancer. [ABSTRACT FROM AUTHOR]

This report was designed to assess the functional role of miR-218/dachshund family transcription factor 1 (DACH1) in diabetic kidney disease (DKD) and investigate its possible molecular mechanism. From the GEO database, we downloaded different datasets for analyzing the expression of miR-218 and DACH1 in DKD. TargetScan was adopted to predict the binding sites between miR-218 and DACH1, which was further verified by dual-luciferase reporter assays. The renal proximal tubule cells (HK-2) treated with high glucose (HG) were used as an in vitro model. QRT-PCR and western blot were used to determine the expression of DACH1 and other relative factors. Cell counting kit-8 and flow cytometer were applied to detect cell viability and apoptosis. The levels of inflammatory cytokines were determined by an ELISA assay. A prominent raise of miR-218 was observed in DKD through bioinformatics analysis, which was further confirmed in the HG-induced model. DACH1 is a target of miR-218. miR-218 reduced cell viability and induced apoptosis by negatively regulating DACH1. Moreover, upregulating miR-218 in HG models increased the concentrations of pro-inflammatory cytokines TNF-α and IL-1β, reduced the level of anti-inflammatory cytokine IL-10, and promoted the epithelial-mesenchymal transition (EMT) process, which is possibly achieved by targeting DACH1. While downregulating miR-218 showed the opposite results. These data demonstrated that, under an in vitro HG environment, miR-218 suppressed the HK-2 cells proliferation, promoted apoptosis, caused an inflammatory response, and facilitated the EMT process largely by targeting DACH1, providing an insight into the therapeutic intervention of DKD. [ABSTRACT FROM AUTHOR]

The need for longitudinal and holistic support of medical students throughout their training has led to the development of formal mentoring programs. Whilst success of formal mentoring programs has been attributed to (a) pairing mentees with trained and experienced mentors (matching), (b) the quality of mentoring interactions and (c) the presence of a nurturing environment, little attention has been attributed to establishing an effective matching process in medical school. We sought, in this review, to redress this gap within the context of matching medical students for mentoring. Modified PRISMA guidelines were followed to guide the review process. PubMed, ERIC, Cochrane Database, OVID and ScienceDirect databases were searched for articles on matching in medical schools and in allied health specialities published between 2000 and 2015. [ABSTRACT FROM AUTHOR]

Assessing the impacts of climate change and human activities on runoff is important for planning and managing water resources and for maintaining the integrity of the ecosystem, as well as the normal operation of modern society. In this study, the distribution of precipitation in the Beichuan River basin from 1961 to 2013 is uneven, and we analyzed the impacts of climate change and human activity on the annual and seasonal runoff change during this period. The results showed that runoff was more sensitive to precipitation than the other meteorological factors during the study period, and a 10% increase in precipitation could increase runoff by 17.5%. The annual runoff showed a downward trend during the past 53 years, with an abrupt change point in 1972. We concluded that human activities were mainly responsible for the runoff reduction, and climate change accounted for approximately 30% of the reduction. For the change in seasonal runoff, the dry season runoff had no significant trend, but there was a downward trend in the wet season runoff, with an abrupt change point in 1998. We concluded that human activities were the dominant cause of the reduction in the wet season runoff (88.27%), and climate change accounted for 11.73% of the reduction. [ABSTRACT FROM AUTHOR]

Objective: Physical education (PE) teachers may be the first to assist students with asthma attacks during PE class. This study explores the PE teachers' perspectives on in-school asthma management and barriers to physical activity (PA) in children with asthma attending urban elementary schools. Methods: We conducted qualitative semi-structured interviews with 16 PE teachers from 10 Bronx, NY elementary schools. Interviews were recorded, transcribed, and independently coded. Content analysis was used to identify 10 major themes common across interviews which were then categorized into 3 domains. Results: Three domains were identified: 1) school procedures and policies for asthma management; 2) role of PE teachers in asthma management; and 3) barriers to PA for students. Most PE teachers were unaware of written procedures for acute asthma management and did not receive asthma-specific training. Many PE teachers expressed confidence regarding asthma management. PE teachers identified students with asthma most commonly through communication with students. The PE teachers utilized various methods to manage asthma but all relied on the nurse to handle acute asthma symptoms. Several barriers to PA were determined, including PE teachers' unawareness of NYS PE requirements, lack of gym facilities, inclement weather, inconsistent PE class time, asthma diagnosis, and having no asthma inhalers at the nurse's office. Conclusions: PE teachers' perspectives on asthma management may influence the way asthma is handled at school. The results from this study highlight several barriers that can be targeted in future interventions to improve asthma management. [ABSTRACT FROM AUTHOR]

Low well-being is common among Chinese pregnant women but few effective interventions currently exist to improve prenatal stress and negative emotions. Mindfulness-based stress reduction (MBSR) has been proved to be effective in reducing stress and rarely studies were focused on Chinese pregnant women. The aim of the current paper is to investigate the effects of 8-week MBSR on prenatal stress, anxiety and depression among Chinese pregnant women. A sample of 66 pregnant women randomly allocated into either the MBSR group (n=34) or the control group (n=32). Participants in the MBSR group received a group 8-week, 90-min each time intervention. The results found a significant interaction between time and condition for prenatal stress (F=45.51, p<0.001, η 2=0.427), anxiety (F=19.30, p<0.001, η 2=0.240), while depression showed no time-by-group interaction (F=0.29, p=0.589, η 2=0.005). As for the sub-scale of state anxiety, while there was only no time effect (F=3.68, p=0.060, η 2=0.057). The findings of this study preliminary indicated effects of the MBSR intervention on self-reported prenatal stress and anxiety in comparison to a treatment-as-usual control. Effect on depression was not observed may due to the low level of depression of participants. This study provides preliminary evidence that MBSR is suitable for Chinese pregnant women and be effective in decreasing prenatal stress, anxiety. [ABSTRACT FROM AUTHOR]

The spindle assembly checkpoint prevents chromosome mis-segregation during mitosis by delaying sister chromatid separation. Several F-box protein members play critical roles in maintaining genome stability and regulating cell cycle progress via ubiquitin-mediated protein degradation. Here, we showed that Fbxo6 critically regulated spindle checkpoint and chromosome segregation. Fbxo6 was phosphorylated during mitosis. Overexpression of Fbxo6 lead to faster exit from nocodazole-induced mitosis arrest through premature sister chromatid separation. Moreover, we found substantially more binuclear and multilobed nuclei cells accompanied with impaired cell viability in Fbxo6-overexpressed HeLa cells. Mechanistically, Fbxo6 interacted with spindle checkpoint proteins including Mad2 and BubR1 leading to the premature exit from mitosis. Overall, we revealed a novel role of Fbxo6 in regulating spindle checkpoint, which may shed light on the regulation of genome instability of cancer cells. [ABSTRACT FROM AUTHOR]

Mentoring in general practice nurtures personal and professional development among mentees and mentors and enhances organisational productivity. Yet, failure to define it leads to variations in understanding and practice and conflation with other educational approaches. As a result, mentoring in general practice is underutilised and poorly overseen. This review seeks to identify elements among successful mentoring relationships to aid the design of local mentoring programmes. Reports of undergraduate and postgraduate mentoring programmes in general practice were analysed thematically. A literature search of mentoring of junior postgraduates or undergraduates by experienced mentors in general practice between 1 January 2000 and 31 December 2015 was done using PubMed, ERIC, ScienceDirect, Cochrane Database of Systematic Reviews and OVID. A total of 1973 abstracts were retrieved and 9 full-text articles were included and analysed. Three themes were identified, including the initiation of mentoring relationships, the mentoring relationship and the mentoring environment. Successful mentoring programmes pivot upon effective mentoring relationships. Based on the themes identified, a framework to guide practice, structure and oversight of the mentoring process is forwarded. Further contextspecific study is needed to ensure the viability of the Mentoring Framework to better employ mentoring in general practice. [ABSTRACT FROM AUTHOR]

A new series of superalkaline-earth-metal compounds Al14X (X = F2, Cl2 , Br2 , I2, (OH)2 , O, S) has been investigated at the TPSS/Def2-TZVPP level. It is found that both interaction position and mode between Al14 and X ligands influence isomer stability of the resulting superatomcompounds. On the one hand, the top and bottomsites of Al14 have higher reactivity relative to middle ones. On the other hand, different ligands favour different binding patterns when combining with Al14. For example, the halogen ligands prefer to occupy on-top sites of Al14. In contrast, the end-on bound configurations are the least favourable ones for Al14 oxide. Natural population analysis indicates that the Al14 cluster donates electrons to X ligands. Atoms in molecules analysis also suggests ionic bond character of the connection(s) between Al14 and X moieties. Thus, the Al14X compounds are much like divalent salts where superatomAl14 behaves just like an alkaline-earth-metal atom. Furthermore, considerable dissociation energies and large highest occupied molecular orbital and lowest unoccupied molecular orbital gaps confirm stability of these superatom compounds. [ABSTRACT FROM AUTHOR]

Cyclin D1 and cyclin E1, as vital regulatory factors of G1-S phase cell cycle progression, are frequently constitutive expressed and associated with pathogenesis and tumorigenesis in most human cancers and they have been regarded as promising targets for cancer therapy. In this study, we established NVP-BEZ235, a potent dual kinase inhibitor, could induce neuroblastoma cells proliferation inhibition without apoptosis activation. Moreover, we showed NVP-BEZ235 could induce neuroblastoma cells arrested at G0/G1 phase accompanied with significant reduction of the cyclin D1 and E1 proteins in a dose dependent manner at nanomole concentration. Additionally we found that GSK3β was dephosphorylated and activated by NVP-BEZ235 and then triggered cyclin D1 and cyclin E1 degradation through ubiquitination proteasome pathway, based on the evidences that NVP-BEZ235 induced downregulation of cyclin D1 and cyclin E1 were obviously recovered by proteasome inhibitor and the blockade of GSK3β contributed to remarkable rescue of cyclin D1 and cyclin E1. Analogous results about its anti-proliferation effects and molecular mechanism were observed on neuroblastoma xenograft mouse model in vivo. Therefore, these results indicate that NVP-BEZ235-induced cyclin D1 and cyclin E1 degradation, which happened through activating GSK3β, and GSK3β-dependent down-regulation of cyclin D1 and cyclin E1 should be available for anticancer therapeutics. [ABSTRACT FROM PUBLISHER]

The widely performance of surfactants is closely related to their interfacial activity, which is essentially determined by the molecular array behaviours at the interface, of which the studies are significance for clearly understanding their structure-performance relationships. In this paper, the detailed molecular array behaviours of green surfactant alkyl polyglycoside (APG) and the mixed systems with other types of surfactants on oil/water interface have been studied using molecular dynamics simulations, and the key theoretical principle was confirmed by quantum chemistry calculations. It was found that the hydrophilic maltose ring head groups of decyl polyglycoside (C10-APG) are prone to lie flatly at the oil-water interface, the steric hindrance results in the low interfacial density, which critically determines the limit of the interfacial activity. The interfacial adsorption behaviours of the binary mixtures of C10-APG and SDS or DATB and the ternary mixtures of C10-APG, SDS and DATB were studied in detail, how the efficient synergism effect could be achieved for the mixture to get super high interfacial activity was discussed. This study provides a strategy to reveal how the molecular interfacial behaviours determine the key interfacial characteristics of the novel surfactants, which might provide help to promote their applications. [ABSTRACT FROM AUTHOR]

The Grand Canonical Monte Carlo (GCMC) and molecular dynamics (MD) simulation methods were used to investigate the adsorption and diffusion properties of CH4 and CO2 in montmorillonite slit-nanopores. It is found that, both CH4 and CO2 could adsorb closely onto the pore surface, while different adsorption states occur for CH4 and CO2, respectively, in montmorillonite slit-nanopores. Competitive adsorption of CO2 over CH4 exists in montmorillonite slit-nanopores, especially at the lower pressures, which is attributed to the different interaction intensity between the CH4-CO2 molecules and the pore surface. The diffusion coefficients of CH4 and CO2 both decrease with the enhanced pressures, while the CO2 has a relative weak diffusion coefficient comparing with CH4. A well displacement of the residual CH4 by CO2 in montmorillonite slit-nanopores was investigated, which is found that the displacement efficiency increases with the enhanced bulk pressures. It was determined that, the CO2 can be captured and reserved in the montmorillonite slit-nanopores during the displacement, and the sequestration amount of CO2 gets enhanced with the bulk pressure increasing. This study provides micro-behaviours of CH4 and CO2 in montmorillonite slit-nanopores, for the purpose to give out useful guidance for enhancing shale gas extraction by injecting CO2. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the expression of lipid peroxidation markers in the tear film and ocular surface and their correlation with disease severity in patients with dry eye disease. Methods: The concentrations of hexanoyl-lysine (HEL), 4-hydroxy-2-nonenal (HNE), and malondialdehyde (MDA) were measured with enzyme-linked immunosorbent assays in tears obtained from 44 patients with non-Sjogren syndrome dry eye and 33 control subjects. The correlations between the marker levels and the tear film and ocular surface parameters, including tear film break-up time (BUT), Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, corneal sensitivity, conjunctival goblet cell density, and symptom score, were analyzed. The expression of the lipid peroxidation markers HEL, 4-HNE, and MDA in the conjunctiva was evaluated using immunohistochemistry. Results: The concentrations of HEL, 4-HNE, and MDA were 279.84 ± 69.98 nmol/L, 0.02 ± 0.01 μg/mL, and 3.80 ± 1.05 pmol/mg in control subjects and 283.21 ± 89.67 nmol/L (p= 0.97), 0.20 ± 0.03 μg/mL (p< 0.01), and 13.32 ± 4.03 pmol/mg (p< 0.01) in dry eye patients. 4-HNE and MDA levels significantly correlated with BUT, Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, conjunctival goblet cell density, and symptom score (p< 0.05), whereas HEL levels did not correlate with these parameters. Staining intensities for 4-HNE and MDA increased in dry eye patients. Conclusions: The expression of late lipid peroxidation markers, 4-HNE and MDA, increases in the tear film and ocular surface of patients with dry eye. The levels correlate with various tear film and ocular surface parameters and may reflect the severity of dry eye disease. [ABSTRACT FROM AUTHOR]

Angiogenesis plays a critical role in the progression of cardiovascular disease, retinal ischemia, or tumorigenesis. The imbalance of endothelial cell proliferation and apoptosis disturbs the establishment of the vasculogenesis, which is affected by several arachidonic acid metabolites. 15-Hydroxyeicosatetraenoic acid (15-HETE) is one of the metabolites. However, the underlying mechanisms of angiogenesis induced by 15-HETE in human umbilical vascular endothelial cells (HUVECs) are still poorly understood. Since extracellular signal-regulated kinase (ERK) is a critical regulator of cell proliferation, there may be a crosstalk between 15-HETE-regulating angiogenic process and ERK-proliferative effect in HUVECs. To test this hypothesis, we study the effect of 15-HETE on cell proliferation, angiogenesis, and apoptosis using cell viability measurement, cell cycle analysis, western blot, scratch–wound, tube formation assay, and nuclear morphology determination. We found that 15-HETE promoted HUVEC angiogenesis, which were mediated by ERK. Moreover, 15-HETE-induced proliferation and cell cycle transition from the G0/G1 phase to the G2/M + S phase. All these effects were reversed after blocking ERK with PD98059 (an ERK inhibitor). In addition, HUVEC apoptosis was relieved by 15-HETE through the ERK pathway. Thus, ERK is necessary for the effects of 15-HETE in the regulation of HUVEC angiogenesis, which may be a novel potential target for the treatment of angiogenesis-related diseases. [ABSTRACT FROM AUTHOR]

Metabolic reprogramming is linked to tumorigenesis, disease progression, clinical outcome and resistance to chemotherapy. However, the significance of glycolytic metabolism in non-Hodgkin lymphoma (NHL) remains unclear. Here we report that both NHL patient-samples and cell lines exhibited significant up-regulation of glycolytic metabolism. The glycolytic inhibitor 2-deoxy- d-glucose (2-DG) inhibited glucose consumption, lactic acid generation and cell proliferation and induced cell cycle arrest in NHL cell lines under both normoxia and hypoxia, and hypoxia could even enhance the inhibitory effects of 2-DG. Furthermore, 2-DG combined with methylprednisolone synergistically inhibited cell proliferation, induced cell apoptosis and cell cycle arrest, and thus increased the sensitivity of NHL cells to methylprednisolone via down-regulation of HIF-1α and c-MYC. In conclusion, these results present a novel insight into critical roles of glycolytic pathway activation in NHL progression and glucocorticoid resistance. Inhibition of the glycolytic pathway may provide a new therapeutic strategy for the treatment of NHL. [ABSTRACT FROM AUTHOR]