Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Mitochondrial Fission and NOX2 Expression Prevent NLRP3 Inflammasome Activation in the Endothelium: The Role of Corosolic Acid Action in the Amelioration of Endothelial Dysfunction.

AIMS Corosolic acid (CRA) is a natural triterpenoid with antioxidative activity. This study was designed to elucidate the mechanism through which CRA protected vessel endothelial homeostasis by combating oxidative stress. RESULTS In endothelial cells, CRA induced dynamin-related protein 1 (Drp1) phosphorylation at Ser637 and thus inhibited mitochondrial fission in response to oxidative stress. It promoted AMP-activated protein kinase (AMPK) activity in an LKB1-dependent manner, and silencing AMPK abrogated its inhibitory effect on Drp1 activation and mitochondrial fission. CRA inhibited the translocation of p47(phox) and p67(phox) and the overexpression of gp91(phox) induced by palmitate (PA), demonstrating its action in suppression of NOX2 activation. Drp1 knockdown reduced PA-induced gp91(phox) expression, while Drp1 induction was also diminished by gp91(phox) knockdown, suggesting the reciprocal relationship between NOX2 and Drp1. Knockdown Drp1 or gp91(phox) attenuated PA-induced NLRP3 induction and enhanced inhibitory effects of CRA. Oral administration of CRA in high-fat diet mice reproduced similar regulation in the aorta endothelium, further confirming its protection on endothelial homeostasis in vivo. INNOVATION This study demonstrated that the defect in mitochondrial morphology is associated with the oxidative stress and NLRP3 inflammasome activation in the endothelium. Drp1 and NOX2 regulated each other and worked together to induce NLRP3 inflammasome activation, suggesting that modulation of Drp1 phosphorylation (Ser637) might be a potential therapeutic target for combating oxidative stress in vessel diseases. CONCLUSION CRA prevented mitochondrial fission by regulation of Drp1 phosphorylation (Ser637) in an AMPK-dependent manner, and this action contributed to blocking NOX2 oxidase signaling and suppressing NLRP3 inflammasome activation in the endothelium. Antioxid. Redox Signal. 24, 893-908.
Inferring user demographics and social strategies in mobile social networks

Demographics are widely used in marketing to characterize different types of customers. However, in practice, demographic information such as age, gender, and location is usually unavailable due to privacy and other reasons. In this paper, we aim to harness the power of big data to automatically infer users' demographics based on their daily mobile communication patterns. Our study is based on a real-world large mobile network of more than 7,000,000 users and over 1,000,000,000 communication records (CALL and SMS). We discover several interesting social strategies that mobile users frequently use to maintain their social connections. First, young people are very active in broadening their social circles, while seniors tend to keep close but more stable connections. Second, female users put more attention on cross-generation interactions than male users, though interactions between male and female users are frequent. Third, a persistent same-gender triadic pattern over one's lifetime is discovered for the first time, while more complex opposite-gender triadic patterns are only exhibited among young people. We further study to what extent users' demographics can be inferred from their mobile communications. As a special case, we formalize a problem of double dependent-variable prediction-inferring user gender and age simultaneously. We propose the WhoAmI method, a Double Dependent-Variable Factor Graph Model, to address this problem by considering not only the effects of features on gender/age, but also the interrelation between gender and age. Our experiments show that the proposed WhoAmI method significantly improves the prediction accuracy by up to 10% compared with several alternative methods.
Resolvin D1 Increases Mucin Secretion in Cultured Rat Conjunctival Goblet Cells via Multiple Signaling Pathways

Purpose Goblet cells in the conjunctiva secrete mucin into the tear film protecting the ocular surface. The proresolution mediator resolvin D1 (RvD1) regulates mucin secretion to maintain homeostasis during physiological conditions and in addition, actively terminates inflammation. We determined the signaling mechanisms used by RvD1 in cultured rat conjunctival goblet cells to increase intracellular [Ca2+] ([Ca2+]i) and induce glycoconjugate secretion. Methods Increase in [Ca2+]i were measured using fura 2/AM and glycoconjugate secretion determined using an enzyme-linked lectin assay with the lectin Ulex Europaeus Agglutinin 1. Signaling pathways activated by RvD1 were studied after goblet cells were pretreated with signaling pathway inhibitors before stimulation with RvD1. The results were compared with results when goblet cells were stimulated with RvD1 alone and percent inhibition calculated. Results The increase in [Ca2+]i stimulated by RvD1 was blocked by inhibitors to phospholipases (PL-) -D, -C, -A2, protein kinase C (PKC), extracellular signal-regulated kinases (ERK)1/2 and Ca2+/calmodulin-dependent kinase (Ca2+/CamK). Glycoconjugate secretion was significantly inhibited by PLD, -C, -A2, ERK1/2 and Ca2+/CamK, but not PKC. Conclusions We conclude that RvD1 increases glycoconjugate secretion from goblet cells via multiple signaling pathways including PLC, PLD, and PLA2, as well as their signaling components ERK1/2 and Ca2+/CamK to preserve the mucous layer and maintain homeostasis by protecting the eye from desiccating stress, allergens, and pathogens.
A Framework for Product Description Classification in E-commerce

We propose the Hierarchical Product Classification (HPC) framework for the purpose of classifying products using a hierarchical product taxonomy. The framework uses a classification system with multiple classification nodes, each residing on a different level of the taxonomy. The innovative part of the framework stems from the definition of classification recipes that can be used to construct high-quality classifier nodes, using the product descriptions in the most optimal way. These classifier recipes are specifically tailored for the e-commerce domain. The use of these classifier recipes enables flexible classifiers that adjust to the taxonomy depth-specific characteristics of product taxonomies. Furthermore, in order to gain insight into which components are required to perform high quality product classification, we evaluate several feature selection methods and classification techniques in the context of our framework. Based on 3000 product descriptions obtained from Amazon.com, HPC achieves an overall accuracy of 76.80% for product classification. Using 110 categories from CircuitCity.com and Amazon.com, we obtain a precision of 93.61% for mapping the categories to the taxonomy of shopping.com.
Interleukin‐6/signal transducer and activator of transcription 3 promotes prostate cancer resistance to androgen deprivation therapy via regulating pituitary tumor transforming gene 1 expression

Prostate cancer can progress from androgen dependence to androgen deprivation resistance with some unknown mechanisms. The current study aims to explore the possible role of pituitary tumor transforming gene1 (PTTG1) in castration‐resistant prostate cancer (CRPC). Initially, we found that PTTG1 expression was significantly increased in androgen‐independent prostate cancer cell lines PC3, DU145 and CRPC specimens compared with that in androgen‐dependent prostate cancer cell line LNCaP and initial prostate cancer specimens. PTTG1 overexpression significantly enhanced the cell survival rate, clonality and tumorigenicity in LNCaP cells upon androgen‐deprivation therapy (ADT). While knockdown of PTTG1 expression significantly elevated the sensitivity of DU145 cells to ADT. The effects of PTTG1 overexpression on LNCaP cells may be ascribed to the induced EMT and increased CD44+CD24‐ cancer stem cell population. Furthermore, we detected that PTTG1 expression was regulated by interleukin‐6 via activated signal transducer and activator of transcription 3 (STAT3) directly binding to the region −500 to +1 of PTTG1 promoter in LNCaP cells. In conclusion, our results elucidate that interleukin‐6/STAT3 activation can increase PTTG1 expression and, consequently, promote the resistance to ADT in CRPC by inducing EMT and increasing the cancer stem cell population, suggesting that PTTG1 may be a novel therapeutic target for CRPC.
A case of mistaken identity: CD11c‐eYFP+ cells in the normal mouse brain parenchyma and neural retina display the phenotype of microglia, not dendritic cells

Under steady‐state conditions the central nervous system (CNS) is traditionally thought to be devoid of antigen presenting cells; however, putative dendritic cells (DCs) expressing enhanced yellow fluorescent protein (eYFP) are present in the retina and brain parenchyma of CD11c‐eYFP mice. We previously showed that these mice carry the Crb1rd8 mutation, which causes retinal dystrophic lesions; therefore we hypothesized that the presence of CD11c‐eYFP+ cells within the CNS may be due to pathology associated with the Crb1rd8 mutation. We generated CD11c‐eYFP Crb1wt/wt mice and compared the distribution and immunophenotype of CD11c‐eYFP+ cells in CD11c‐eYFP mice with and without the Crb1rd8 mutation. The number and distribution of CD11c‐eYFP+ cells in the CNS was similar between CD11c‐eYFP Crb1wt/wt and CD11c‐eYFP Crb1rd8/rd8 mice. CD11c‐eYFP+ cells were distributed throughout the inner retina, and clustered in brain regions that receive input from the external environment or lack a blood‐brain barrier. CD11c‐eYFP+ cells within the retina and cerebral cortex of CD11c‐eYFP Crb1wt/wt mice expressed CD11b, F4/80, CD115 and Iba‐1, but not DC or antigen presentation markers, whereas CD11c‐eYFP+ cells within the choroid plexus and pia mater expressed CD11c, I‐A/I‐E, CD80, CD86, CD103, DEC205, CD8α and CD135. The immunophenotype of CD11c‐eYFP+ cells and microglia within the CNS was similar between CD11c‐eYFP Crb1wt/wt and CD11c‐eYFP Crb1rd8/rd8 mice; however, CD11c and I‐A/I‐E expression was significantly increased in CD11c‐eYFP Crb1rd8/rd8 mice. This study demonstrates that the overwhelming majority of CNS CD11c‐eYFP+ cells do not display the phenotype of DCs or their precursors and are most likely a subpopulation of microglia. GLIA 2016. GLIA 2016;64:1331–1349
Lowering minimum eye height to increase peak knee and hip flexion during landing

ABSTRACT The purpose was to determine the effect of lowering minimum eye height through an externally focused object on knee and hip flexion and impact forces during jump-landing. Kinematics and ground reaction forces were collected when 20 male and 19 female participants performed jump-landing trials with their natural minimum eye height, and trials focusing on lowering their minimum eye height to an external object, which was set at 5% or 10% of standing height lower. Participants demonstrated decreased minimum eye height and increased peak knee and hip flexion during early-landing and stance phase when focusing on lowering eye height to the external object (p < 0.01). Peak vertical ground reaction forces during early-landing also decreased for the greater force group (p < 0.001). Jump-landing training through manipulating eye height provides a strategy that involves an external focus and intrinsic feedback, which may have advantages in promoting learning and practical application.
Polymyxin B effects on motility parameters of cryopreserved bull semen

Objective: To evaluate the effect of adding different values of polymyxin B (PMB) to bull semen on various motility parameters of post-thawed semen such as total motility, progressive motility and velocity parameters using kinetic parameters of sperm by Computer Assisted Sperm Analysis. Methods: Gram negative bacteria release lipopolysaccharide, which induces the apoptotic pathway. Antibiotics are added to semen in order to prevent bacterial contaminations in bovine semen. These antibiotics kill the bacteria especially gram negative bacteria. Therefore, their endotoxins are released during bacteriolysis and bind to the head region and midpiece of sperm. PMB is a bactericidal antibiotic against multidrug resistant gram-negative bacteria and is able to neutralize the toxic effects of the released endotoxin. This study was performed on 3-year old Taleshi bulls. Results: The results showed both positive and negative significant effects of PMB on semen quality. Total motility and progressive motility were significantly increased (P<0.000 1) by 100 μg per mL of PMB (55.2% and 48.8% respectively) against the control groups (43.5% and 37.7%, respectively). Moreover, they were significantly decreased (P<0.000 1) by 1 000 μg per mL of PMB (35.2% and 28.8% respectively) against the control groups (43.5% and 37.7% respectively) in above-mentioned parameters. In Computer Assisted Semen Analyzer, parameter VAP was significantly decreased (P<0.04) in 1 000 μg (69.6 μm/s) against the control group (78.7 μm/s). Finally, using PMB in processing cryopreserved bull semen is advised, but before using it, the rate of endotoxins must be measured. Conclusions: We advise using PMB after measuring endotoxin concentration; In vitro, in vivo and in field fertilization, adding other sperm evaluation factors such as acrosomal integrity, DNA integrity, mitochondrial function to PMB treated semen.
Antiphosphatidylserine/prothrombin antibodies (aPS/PT) as potential diagnostic markers and risk predictors of venous thrombosis and obstetric complications in antiphospholipid syndrome

Abstract Background: The aim of the study was to determine the prevalence and clinical associations of antiphosphatidylserine/prothrombin antibodies (aPS/PT) with thrombosis and pregnancy loss in Chinese patients with antiphospholipid syndrome (APS) and seronegative APS (SNAPS). Methods: One hundred and eighty six Chinese patients with APS (67 primary, 119 secondary), 48 with SNAPS, 176 disease controls (79 systemic lupus erythematosus [SLE], 29 Sjogren’s syndrome [SS], 30 ankylosing spondylitis [AS], 38 rheumatoid arthritis [RA]) and 90 healthy donors were examined. IgG and IgM aPS/PT, IgG/IgM/IgA anticardiolipin (aCL) and IgG/IgM/IgA anti-β2-glycoprotein I (anti-β2GPI) antibodies were tested by ELISA. Results: One hundred and sixty (86.0%) of APS patients were positive for at least one aPS/PT isotype. One hundred and thirty five (72.6%) were positive for IgG aPS/PT, 124/186 (66.7%) positive for IgM aPS/PT and 99 (53.2%) positive for both. Approximately half of the SNAPS patients were positive for IgG and/or IgM aPS/PT. Highly significant associations between IgG aPS/PT and venous thrombotic events (odds ratio [OR]=6.72) and IgG/IgM aPS/PT and pregnancy loss (OR=9.44) were found. Levels of IgM aPS/PT were significantly different in APS patients with thrombotic manifestations and those with fetal loss (p=0.014). The association between IgG/IgM aPS/PT and lupus anticoagulant (LAC) was highly significant (p<0.001). When both were positive, the OR for APS was 101.6. Notably, 91.95% (80/87) of LAC-positive specimens were positive for IgG and/or IgM aPS/PT, suggesting aPS/PT is an effective option when LAC testing is not available. Conclusions: Anti-PS/PT antibody assays demonstrated high diagnostic performance for Chinese patients with APS, detected some APS patients negative for criteria markers and may serve as potential risk predictors for venous thrombosis and obstetric complications.
IL-35 induces N2 phenotype of neutrophils to promote tumor growth

IL-35 is an immunosuppressive cytokine and exerts regulatory effects on T cells, B cells, macrophages and dendritic cells. Neutrophils are important innate immune cells that play key roles in tumor development. The effect of IL-35 on neutrophils remains unknown. Here, we report that IL-35 can induce N2 neutrophil polarization (protumor phenotype) by increasing G-CSF and IL-6 production, and promote neutrophil infiltration into tumor microenvironment. The sustained expression of IL-35 could promote chronic inflammation to augment the proangiogenic and immunosuppressive function of neutrophils. IL-35 stimulated macrophages to secrete proinflammatory cytokines IL-1β and IL-6. IL-1β stimulated γδ T cells to produce IL-17, which in turn increased the production of G-CSF. By increasing the expression of G-CSF and IL-6, IL-35 could up-regulate the expression of MMP-9 and Bv8, and down-regulate TRAIL expression in neutrophils, thus augmenting the proangiogenic function of neutrophils. Moreover, G-CSF/IL-6 induced the enhanced activation of STAT3 and ERK pathways in neutrophils, thus increasing the expression of iNOS to suppress T cell activation. Our findings suggest that IL-35 can promote tumor progression by functioning as an up-stream cytokine to promote cancer-associated inflammation and control neutrophil polarization. Targeting IL-35 might be an important approach for designing new strategy of tumor therapy.
INVESTIGATION OF FORMABILITY OF LOW CARBON STEEL SHEETS BY FORMING LIMIT DIAGRAMS

Low carbon steel sheets have many applications in industries, especially in automotive parts, therefore it is necessary to study formability of these steel sheets. Forming limit diagram (FLD) is one of the strong pieces of equipment used to study the formability of sheet metals. In this study, FLDs have been determined experimentally for three grades ST12, ST14, and Interstitial free (IF) by conducting punch-stretching experiments using suitably designed and fabricated tools. Formability observed from FLDs has been correlated with mechanical properties and formability parameters like punch type, punch diameter, friction between punch and sheet, work hardening exponent (n) and plane-anisotropy (r) of the sheets. Results have indicated that forming strains in IF and ST14 steel sheets are higher than ST12 and higher n×r values and thickness are desirable to raise the forming strains. The sheet orientation can be effective and in addition, depends on the strain path . For example, forming limit strains in 45 angles with respect to the rolling direction are less than that for 0 and 90 within the right band of FLDs. Keywords– Forming limit diagram, formability, r, n values, low carbon steel
Mechanical properties and morphology of hot drawn polyacrylonitrile nanofibrous yarn

In this study PAN nanofibrous yarn was produced by two-nozzle conjugated electrospinning method. The nanofibrous yarns were drawn continuously in boiling water with drawing ratios of 1, 2, 3, and 4. The morphology of drawn yarns was investigated by scanning electron microscopy and tested for tensile properties as well as untreated yarn. The results showed that the nanofiber alignment in the yarn axis direction, the tensile strength, and tensile modulus of yarn increases as a result of drawing while the tensile strain and work of rapture decrease. X-ray diffraction patterns of the produced yarns were analyzed as well. It was found that crystallinity index increases as the draw ratio increases. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
Detection of Huanglongbing (Citrus Greening) Disease by Nucleic Acid Spot Hybridization

Polymerase chain reaction (PCR) amplification with primers specific to the rDNA region successfully amplified the 1160-bp DNA fragment from a Huanglongbing (HLB)-infected sweet orange sample with mottling symptoms leaves, but not from healthy sweet orange plants. The PCR product of 1160-bp was used as probe labeled with biotin for detection of the HLB pathogen in the nucleic acid spot hybridization (NASH) test. It was found that the HLB pathogen could be detected up to 1:100 dilution in HLB-infected tissue. Total DNA extracted from HLB-infected tissue was diluted 2-fold as 900 ng in TE buffer and spotted on a nitrocellulose membrane. Strong signals were observed up to 225 ng of DNA dilution, whereas a moderate signal was recorded at 112 ng. No hybridization signal was observed in the healthy samples, while strong signals were observed in the positive control
Cho Endonuclease Functions during DNA Interstrand Cross-Link Repair in Escherichia coli

ABSTRACT DNA interstrand cross-links are complex lesions that covalently link both strands of the duplex DNA. Lesion removal is proposed to be initiated via the UvrABC nucleotide excision repair complex; however, less is known about the subsequent steps of this complex repair pathway. In this study, we characterized the contribution of nucleotide excision repair mutants to survival in the presence of psoralen-induced damage. Unexpectedly, we observed that the nucleotide excision repair mutants exhibit differential sensitivity to psoralen-induced damage, with uvrC mutants being less sensitive than either uvrA or uvrB. We show that Cho, an alternative endonuclease, acts with UvrAB and is responsible for the reduced hypersensitivity of uvrC mutants. We find that Cho's contribution to survival correlates with the presence of DNA interstrand cross-links, rather than monoadducts, and operates at a step after, or independently from, the initial incision during the global repair of psoralen DNA adducts from the genome. IMPORTANCE DNA interstrand cross-links are complex lesions that covalently bind to both strands of the duplex DNA and whose mechanism of repair remains poorly understood. In this study, we show that Cho, an alternative endonuclease, acts with UvrAB and participates in the repair of DNA interstrand cross-links formed in the presence of photoactivated psoralens. Cho's contribution to survival correlates with the presence of DNA interstrand cross-links and operates at a step after, or independently from, the initial incision during the repair process.
Genetic Inhibition of Receptor Interacting Protein Kinase-1 Reduces Cell Death and Improves Functional Outcome After Intracerebral Hemorrhage in Mice

Background and Purpose— Recent studies using cultured cells and rodent intracerebral hemorrhage (ICH) models have implicated RIPK1 (receptor interacting protein kinase-1) as a driver of programmed necrosis and secondary injury based on use of chemical inhibitors. However, these inhibitors have off-target effects and cannot be used alone to prove a role for RIPK1. The aim of the current study was to examine the effect of genetic inhibition of the kinase domain of RIPK1 in a mouse ICH model. Methods— We subjected 2 lines of mice with RIPK1 point mutations of the kinase domain (K45A and D138N), rendering them kinase inactive, to autologous blood ICH and measured acute cell death and functional outcome. Results— Compared with wild-type controls, RIPK1K45A/K45A and RIPK1D138N/D138N had significantly less cells with plasmalemma permeability, less acute neuronal cell death, less weight loss and more rapid weight gain to baseline, and improved performance in a Morris water maze paradigm after autologous blood ICH. In addition, mice systemically administered GSK′963, a potent, specific, brain penetrant small molecule RIPK1 inhibitor, had reduced acute neuronal death at 24 hours after ICH. Conclusions— The data show that the kinase domain of RIPK1 is a disease driver of ICH, mediating both acute cell death and functional outcome, and support development of RIPK1 inhibitors as therapeutic agents for human ICH.