Miracle-dz/UniFAR-FTUs huggingface dataset:
Scutellarin Suppresses NLRP3 Inflammasome Activation in Macrophages and Protects Mice against Bacterial Sepsis

The NLRP3 inflammasome plays a critical role in mediating the innate immune defense against pathogenic infections, but aberrant activation of NLRP3 inflammasome has been linked to a variety of inflammatory diseases. Thus targeting the NLRP3 inflammasome represents a promising therapeutic for the treatment of such diseases. Scutellarin is a flavonoid isolated from Erigeron breviscapus (Vant.) Hand. -Mazz. and has been reported to exhibit potent anti-inflammatory activities, but the underlying mechanism is only partly understood. In this study, we aimed to investigate whether scutellarin could affect the activation of NLRP3 inflammasome in macrophages. The results showed that scutellarin dose-dependently reduced caspase-1 activation and decreased mature interleukin-1β (IL-1β) release in lipopolysaccharide (LPS)-primed macrophages upon ATP or nigericin stimulation, indicating that scutellarin inhibited NLRP3 inflammasome activation in macrophages. Consistent with this, scutellarin also suppressed pyroptotic cell death in LPS-primed macrophages treated with ATP or nigericin. ATP or nigericin-induced ASC speck formation and its oligomerization were blocked by scutellarin pre-treatment. Intriguingly, scutellarin augmented PKA-specific phosphorylation of NLRP3 in LPS-primed macrophages, which was completely blocked by selective PKA inhibitor H89, suggesting that PKA signaling had been involved in the action of scutellarin to suppress NLRP3 inflammasome activation. Supporting this, the inhibitory effect of scutellarin on NLRP3 inflammasome activation was completely counteracted by H89 or adenyl cyclase inhibitor MDL12330A. As NLRP3-dependent release of IL-1β has a critical role in sepsis, the in vivo activity of scutellarin was assayed in a mouse model of bacterial sepsis, which was established by intraperitoneally injection of a lethal dose of viable Escherichia coli. Oral administration of scutellarin significantly improved the survival of mice with bacterial sepsis. In line with this, scutellarin treatment significantly reduced serum IL-1β levels and attenuated the infiltration of inflammatory cells in the liver of E. coli-infected mice. These data indicated that scutellarin suppressed NLRP3 inflammasome activation in macrophages by augmenting PKA signaling, highlighting its potential therapeutic application for treating NLRP3-related inflammatory diseases.
Systematic review of patient-reported outcome measures for functional performance in the lower limb.

OBJECTIVE To identify psychometrically evaluated patient-reported outcome measures reflective of 'real-life' function (active and passive) for application following focal rehabilitation interventions in the lower limb after stroke or brain injury. DATA SOURCES A literature search conducted in MEDLINE, CINAHL, Embase, Web of Science, PubMed, National Health Service National Research Register, MRC Clinical Trials directory, Database of Abstracts of Reviews of Effects (DARE), Google Scholar and the Cochrane Database of Systematic Reviews. STUDY SELECTION Interventional study designs using patient-reported outcome measures for outcome evaluation meeting the review objective. DATA EXTRACTION Evaluation of the psychometric properties used the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) process, by two independent reviewers reaching consensus, with adjudication by a third reviewer. DATA SYNTHESIS One-hundred and thirteen studies were identified following initial review of the abstracts, yielding 12 outcome measures. Eight measures were identified, which were relevant to real life functional performance. These were the Brain Injury Community Rehabilitation Outcome, Climbing Stairs Questionnaire, Human Activity Profile, Lower Extremity Functional Scale, Nottingham Extended ADL Index, Rivermead Mobility Index (RMI), Sickness Impact Profile, Stroke Impact Scale. CONCLUSIONS All measures addressed active function, with none evaluating passive function. The RMI met most psychometric criteria, but may have a ceiling effect for high functioning patients.
Disruption of the ribosomal P complex leads to stress-induced autophagy

The human ribosomal P complex, which consists of the acidic ribosomal P proteins RPLP0, RPLP1, and RPLP2 (RPLP proteins), recruits translational factors, facilitating protein synthesis. Recently, we showed that overexpression of RPLP1 immortalizes primary cells and contributes to transformation. Moreover, RPLP proteins are overexpressed in human cancer, with the highest incidence in breast carcinomas. It is thought that disruption of the P complex would directly affect protein synthesis, causing cell growth arrest and eventually apoptosis. Here, we report a distinct mechanism by which cancer cells undergo cell cycle arrest and induced autophagy when RPLP proteins are downregulated. We found that absence of RPLP0, RPLP1, or RPLP2 resulted in reactive oxygen species (ROS) accumulation and MAPK1/ERK2 signaling pathway activation. Moreover, ROS generation led to endoplasmic reticulum (ER) stress that involved the EIF2AK3/PERK-EIF2S1/eIF2α-EIF2S2-EIF2S3-ATF4/ATF-4- and ATF6/ATF-6-dependent arms of the unfolded protein response (UPR). RPLP protein-deficient cells treated with autophagy inhibitors experienced apoptotic cell death as an alternative to autophagy. Strikingly, antioxidant treatment prevented UPR activation and autophagy while restoring the proliferative capacity of these cells. Our results indicate that ROS are a critical signal generated by disruption of the P complex that causes a cellular response that follows a sequential order: first ROS, then ER stress/UPR activation, and finally autophagy. Importantly, inhibition of the first step alone is able to restore the proliferative capacity of the cells, preventing UPR activation and autophagy. Overall, our results support a role for autophagy as a survival mechanism in response to stress due to RPLP protein deficiency.
The Impact of High Anxiety Level on Cellular and Humoral Immunity in Mice

Background/Aims: In the present study, we aimed to examine whether a high anxiety level affects various parameters of immunity in mice. Methods: We used the behavioral light/dark choice test to evaluate whether high anxiety has an impact on various parameters of cellular (granulocytes, monocytes, total lymphocytes, TCD4+, TCD8+ and NK numbers) and humoral (IgA, E and G concentrations) immunity. Secondly, we investigated whether the cellular and humoral immune systems of mice with contrasting levels of anxiety responded differently to stressors (such as physical restraint) by monitoring blood markers of the both types of immunity. Results: High levels of anxiety inhibited part of the cellular and humoral immune systems by significantly decreasing total lymphocytes numbers (including TCD4+ and TCD8+) and immunoglobulin (A and E) concentrations. However, no significant changes in the number of granulocytes, monocytes or NK cells were observed. As a consequence, overall, our results suggest that high anxiety led to a decrease in the efficiency of the immune system of anxious mice. On the other hand, our findings also showed that restraint stress (acute and subacute) produced the same immunological profile as high anxiety in mice. This was independent of the animals’ anxiety status. At the same time, we observed that restraint stress produced significant increases in the levels of granulocytes and monocytes. Conclusions: High anxiety and restraint stress exerted adverse effects on cellular and humoral immunity in mice. While the effect of restraint stress was independent of the anxiety levels in mice, this stress led to an aggravation of the immune response from the high degree of anxiety. Therefore, anxious subjects could be more vulnerable to infections and inflammation, particularly when they are exposed to stressful situations.
Implication of Human Endogenous Retroviruses in the Development of Autoimmune Diseases

Retroviruses can exist in an endogenous form, in which viral sequences are integrated into the human germ line and are vertically transmitted in a Mendelian fashion. Human endogenous retroviruses (HERVs), probably representing footprints of ancient germ-cell retroviral infections, occupy about 1% of the human genome. Some HERVs emerged in the genome over 25 million years ago, while others have appeared rather recently, at about the time of hominid and ape lineages divergence. Although some of these elements show mutations and deletions, some HERVs are transcriptionally active and produce functional proteins. Some medical conditions, such as cancer and autoimmune diseases, are linked to the transcription of some of the HERVs genes, to the expression of HERVs proteins (that may act as superantigens, for example), and/or to the development of antibodies against them that might cross-react with our own proteins. Their genetic sequences may also be, totally or partially, integrated into genes that regulate the immune response. These mechanisms could give rise to autoimmune diseases, such as lupus erythematosus, insulin-dependent diabetes mellitus, multiple sclerosis, Sjögren's syndrome, and rheumatoid arthritis, among others. This review is aimed at discussing evidence for a possible role of HERVs in the etiopathogenesis of different autoimmune diseases.
Depression, Mood State, and Back Pain During Microgravity Simulated by Bed Rest

Objective The objective of this study was to develop a ground-based model for spinal adaption to microgravity and to study the effects of spinal adaptation on depression, mood state, and pain intensity. Methods We investigated back pain, mood state, and depression in six subjects, all of whom were exposed to microgravity, simulated by two forms of bed rest, for 3 days. One form consisted of bed rest with 6 degrees of head-down tilt and balanced traction, and the other consisted of horizontal bed rest. Subjects had a 2-week period of recovery between the studies. The effects of bed rest on pain intensity in the lower back, depression, and mood state were investigated. Results Subjects experienced significantly more intense lower back pain, lower hemisphere abdominal pain, headache, and leg pain during head-down tilt bed rest. They had higher scores on the Beck Depression Inventory (ie, were more depressed) and significantly lower scores on the activity scale of the Bond-Lader questionnaire. Conclusions Bed rest with 6 degrees of head-down tilt may be a better experimental model than horizontal bed rest for inducing the pain and psychosomatic reactions experienced in microgravity. Head-down tilt with balanced traction may be a useful method to induce low back pain, mood changes, and altered self-rated activity level in bed rest studies.
Correlation analysis of gastroesophageal reflux disease and obstructive sleep apnea hypopnea syndrome

Objective: This study aimed to investigate the sleep quality and sleep respiratory conditions at night in patients with various level of gastroesophageal reflux disease (GERD) before and after conventional treatments. Methods: 40 patients with GERD were further divided into the non-erosive reflux disease (NERD) group and the reflux esophagitis (RE) group. 20 healthy people were enrolled as control group. The Pittsburgh Sleep Quality Index (PSQI) was used for evaluate sleep quality and video polysomnography (PSG) was used to assess the sleep respiratory conditions in all patients. PSG was rechecked at the third month after treatment, and the variation of apnea hypopnea index (AHI), the lowest oxygen saturation (LSaO2), mean oxygen saturation (MSaO2), and wakening times (WT) before and after treatments were detected. Results: There were significant differences of PSQI scores between GERD group and healthy control group (P<0.05). GERD could increase the incidence of obstructive sleep apneahypopnea syndrome (OSAHS), but its severity was not associated with the degree of OSAHS. There was no significant difference of OSAHS incidence and severity between RE group and NERD group (P>0.05). Furthermore, there was significant difference of the variation of MSaO2, frequency of awakening and apnea hypopnea, LSaO2 and AHI in RE and NERD group before and after treatments, but no significant difference of the OSAHS incidence. Conclusion: There is sleep apnea with variant degrees in GERD patients, and the sleep apnea can be improved after the GERD controlled.
The effects of a static magnetic field on DNA synthesis and survival of mammalian cells irradiated with fast neutrons

The effects of a static magnetic field (0.75 T) on DNA synthesis and survival were examined with Chinese hamster V79 cells in cultures with and without fast‐neutron irradiation. We found that the magnetic field applied alone for up to several hours did not cause a significant effect in either the rate of DNA synthesis or cell viability; the latter was assayed by colony formation. When cells were exposed simultaneously to the magnetic field and fast neutrons, the effects resembled those observed with neutrons alone. This was the case for both inhibition of DNA synthesis and cell killing. Cells irradiated first with neutrons followed immediately by 1 h of magnetic field exposure showed a dose‐survival response curve indistinguishable from that of neutrons alone. These data suggest that the biological effect due to the magnetic field is negligible and that the presence of the magnetic field either during or subsequent to fast‐neutron irradiation does not affect the neutron‐induced radiation damage or its repair. © 1987 Academic Press, Inc.
Patch Map for Fast Texture Synthesis

A novel texture synthesis method is presented to form large and feature-preserved textures. The task of texture synthesis is divided into two phases: analysis, and synthesis. During the analysis phase, we generate a patch map via Graph cuts, feature deformation and matching. The main task of synthesis phase is to pick up a patch in the patch map and place it in the output to synthesize large target textures. The experimental results show that the patch map algorithm fast synthesizes high-quality textures ranging from regular to stochastic. Compared with the existing methods, our approach preserves texture feature well when pixel-based jump map algorithm and graph cuts method fail to produce good results.
Model-Based Multiple Instance Learning

While Multiple Instance (MI) data are point patterns -- sets or multi-sets of unordered points -- appropriate statistical point pattern models have not been used in MI learning. This article proposes a framework for model-based MI learning using point process theory. Likelihood functions for point pattern data derived from point process theory enable principled yet conceptually transparent extensions of learning tasks, such as classification, novelty detection and clustering, to point pattern data. Furthermore, tractable point pattern models as well as solutions for learning and decision making from point pattern data are developed.
All work and no play? The sociology of women and leisure

Make more knowledge even in less time every day. You may not always spend your time and money to go abroad and get the experience and knowledge by yourself. Reading is a good alternative to do in getting this desirable knowledge and experience. You may gain many things from experiencing directly, but of course it will spend much money. So here, by reading all work and no play the sociology of women and leisure, you can take more advantages with limited budget.
Luminosity segregation in three clusters of galaxies (A119, A2443, A2218)

We use deep wide-field V-band imaging obtained with the Wide Field Camera at the prime focus of the Issac Newton Telescope to study the spatial and luminosity distribution of galaxies in three low redshift (0.04 < z < 0.2) clusters: Abell 119, Abell 2443 and Abell 2218. The absolute magnitude limits probed in these clusters are M V - 5 log h 0.7 = -13.3, -15.4 and -16.7 mag, respectively. The galaxy population, at all luminosities, along the line-of-sight to the clusters can be described by the linear combination of a King profile and a constant surface density of field galaxies. We find that, for these three clusters, the core radius is invariant with intrinsic luminosity of the cluster population to the above limits and thus there is no evidence for luminosity segregation in these clusters. The exception is the brightest galaxies in A2218 which exhibit a more compact spatial distribution. We find that the total projected luminosity distribution (within 1 h -1 0.7 Mpc of the cluster centre) can be well represented by a single Schechter function with moderately flat faint-end slopes: a = -1.22 +0.07 -0.06 (A119), a = -1.11 +0.10 -0.09 (A2443) and α = -1.14 +0.08 -0.07 (A2218). We perform a geometric deprojection of the cluster galaxy population and confirm that no 'statistically significant' evidence of a change in the shape of the luminosity distribution with cluster-centric radius exists. Again, the exception being A2218 which exhibits a core region with a flatter faint-end slope.
Acquiescence or Activism? Political Behavior among the Politically Alienated

This paperfocuses on factors associated with mass society and relative deprivation theories as determinants of political behavior among the politically alienated. Results from contingency table and logit analysis suggest that not only do the alienated differ from their nonalienated counterparts, but also there are substantial variations among the alienated: (1) those with organizational affiliations and trust in others are less likely to be "political dropouts"; (2) those who feel worse off or underemployed are less likely to be "political ritualists"; (3) those with organizational affiliations are more likely to engage simultaneously in conventional and unconventional modes of participation; and (4) those who are untrusting and those who feel underemployed are significantly more likely to be involved as protestors. Mass society and relative deprivation theories help distinguish among the politically alienated, but their predictions about the relative frequencies of different reactions to alienation are not borne out.
New Therapeutic Options for Autism Spectrum Disorder: Experimental Evidences

Autism spectrum disorder (ASD) is characterized by impairment in two behavioral domains: social interaction/communication together with the presence of stereotyped behaviors and restricted interests. The heterogeneity in the phenotype among patients and the complex etiology of the disorder have long impeded the advancement of the development of successful pharmacotherapies. However, in the recent years, the integration of findings of multiple levels of research, from human genetics to mouse models, have made considerable progress towards the understanding of ASD pathophysiology, allowing the development of more effective targeted drug therapies. The present review discusses the current state of pharmacological research in ASD based on the emerging common pathophysiology signature.
Crafting the Change: The Role of Employee Job Crafting Behaviors for Successful Organizational Change

Organizations today have to change constantly. Although both practitioners and scientists agree that organizational change communication is the most effective strategy to improve employee adjustment to change, little is known about how change communication enhances more proactive employee reactions to change. The present study addresses employee job crafting behaviors (i.e., seeking job resources, seeking job challenges, and reducing job demands) as a tool used by employees in order to respond to and cope with implemented organizational change. Using regulatory focus theory, we propose that on the basis of their promotion or prevention regulatory focus, employees respond to organizational change communication via job crafting behaviors that further enhance or hinder their adjustment to change (i.e., work engagement and adaptivity). Hypotheses are tested with a latent change score analytical approach via a three-wave longitudinal design among 368 police officers. Findings reveal that while adequate change communication is linked to increased job crafting behaviors for promotion focused employees, inadequate change communication is linked to increased job crafting behaviors for prevention focused employees. Furthermore, seeking resources is positively associated with employee work engagement, seeking challenges is positively associated with adaptivity, and reducing demands is negatively associated with work engagement. These findings bring together three different streams of literature (i.e., organizational change, regulatory focus, and job crafting). Implications for management are outlined, and they are, thereafter, translated to a specific workplace intervention, which is proposed to organizations and managers.
A phase I study to determine the safety, tolerability and maximum tolerated dose of green-lipped mussel (Perna canaliculus) lipid extract, in patients with advanced prostate and breast cancer.

BACKGROUND This was a phase I trial to determine the maximum tolerated dose (MTD) of a marine lipid extract from the New Zealand green-lipped mussel (Perna canaliculus), as an inhibitor of 5- and 12-lipo-oxygenase enzymes, in patients with advanced breast and prostate cancers. PATIENTS AND METHODS This was an open-labelled, phase I, dose-escalation study. Proprietary form of green-lipped mussel lipid extract (GLMLE), 260-mg capsule, was administered on a twice-daily schedule, orally. Patients remained on study until disease progression or unacceptable toxicity. RESULTS From December 1999 to May 2003, 17 patients were enrolled. Fifteen of them were male with advanced prostate cancer and two were female with advanced breast cancer. The median age of the patients was 74 years (range 56-85 years). Sixteen patients were assessable for adverse events and dose-limiting toxicity (DLT). Reason for withdrawal from the study included progressive disease (n = 12), death (n = 1) and DLT (n = 3). Two patients had evidence of grade 4 hepatic dysfunction. The MTD was not reached. There were no objective tumour responses noted. CONCLUSIONS GLMLE appears to be a well-tolerated compound in this setting. There appears to be no objective benefit. However, grade 3/4 hepatic toxicity noted in two patients is of concern and should be considered while evaluating patients taking GLMLE or while designing studies with this agent.
Links among the Self, Stress, and Psychological Distress during Emerging Adulthood: Comparing Three Theoretical Models

Abstract The authors tested three theoretical models linking self, stress, and psychopathological distress in emerging adulthood. The vulnerability model posits that self-concept pathology leads to distress. The scarring model postulates that distress and stress lead to self-concept pathology. The stress generation model stipulates that distress and self-concept pathology lead to the experience of episodic and chronic life stress. Change in ruminative brooding was examined as a potential mechanism in all models. One-hundred and seventy Israeli freshmen (M[age] = 23.19, 68% females) were followed up three times over the duration of one year. Distress and six dimensions of the self (self-criticism, self-concept inadequacy, hated sense of self, self-esteem, generalized self-efficacy, and self-concept clarity) were assessed repeatedly. Acute and chronic stresses were measured at Time 2 using the University of California, Los Angeles (UCLA) Stress Interview. Distress prospectively predicted self-concept pathology pertaining to all of the dimensions, except self-concept clarity, which was adversely affected by chronic stress. Change in ruminative brooding mediated scarring for self-criticism, a hated self, and self-concept clarity. Low self-esteem emerged as a powerful chronic stress generator. Self-concept clarity was as the only dimension leading to change in distress. In emerging adulthood, psychological distress and—to a lesser extent—chronic stress might “scar” the self.