Miracle-dz/UniFAR-FTUs huggingface dataset:
Dapagliflozin attenuates cholesterol overloading-induced injury in mice hepatocytes with type 2 diabetes mellitus (T2DM) via eliminating oxidative damages

ABSTRACT Cholesterol overloading-induced damages on hepatocytes cause liver dysfunctions, which further damages cholesterol metabolism and results in visceral fat accumulation in patients with type 2 diabetes mellitus (T2DM). The sodium-glucose cotransporter 2 (SGLT2) inhibitor Dapagliflozin has been reported to regulate cholesterol levels in T2DM patients, but the underlying mechanisms have not been studied. In the present study, we initially established in vivo T2DM mice models, and our results showed that both free cholesterol (FC) and cholesteryl ester (CE) were accumulated, while the pro-proliferation associated genes were downregulated in T2DM mice liver tissues, which were reversed by Dapagliflozin co-treatment. Similarly, the mice primary hepatocytes were loaded with cholesterol to establish in vitro models, and we expectedly found that Dapagliflozin attenuated cholesterol-overloading induced cytotoxicity and cellular senescence in the hepatocytes. Then, we noticed that oxidative damages occurred in T2DM mice liver tissues and cholesterol treated hepatocytes, which could be suppressed by Dapagliflozin. Also, elimination of Reactive Oxygen Species (ROS) by N-acetyl-L-cysteine (NAC) recovered cellular functions of hepatocytes in vitro and in vivo. Furthermore, the potential underlying mechanisms were uncovered, and our data suggested that Dapagliflozin activated the anti-oxidant Nrf2/HO-1 pathway in mice hepatocytes, and silencing of Nrf2 abrogated the protective effects of Dapagliflozin on cholesterol-overloaded hepatocytes. Collectively, we concluded that Dapagliflozin recovered cholesterol metabolism functions in T2DM mice liver via activating the anti-oxidant Nrf2/HO-1 pathway, and our data supported that Dapagliflozin was a potential therapeutic drug to eliminate cholesterol-induced cytotoxicity during T2DM pathogenesis.
Nutritional components and protein quality analysis of genetically modified phytase maize

ABSTRACT The nutritional components and protein quality of genetically modified maize expressing phytase gene (GM) were analyzed and evaluated in this study. The nutritional components were analyzed by Chinese national standard methods. The ileostomy Bama miniature pigs were utilized to analyze the true digestibility of protein and amino acids. The digestible indispensable amino acid score (DIAAS) was adopted to evaluate the protein quality of GM, its parental maize (PM) and commercial available maize Zhengdan 958 (ZD). Meanwhile, the widely used protein digestibility corrected amino acid score (PDCAAS) was also calculated and compared with DIAAS. The content of protein, fat, vitamins, and minerals of all the strains of maize are in the normal ranges of OECD and/or ILSI. The DIAAS of GM, PM, and ZD were 54.57, 31.75, and 33.91, respectively, and the first limiting amino acid for GM, PM, and ZD was lysine. In conclusion, the introduction of phyA2 gene in GM maize does not disturb the digestion of protein/amino acid, but has the ability to promote the digestion of amino acids.
Bidirectional Association Between Obsessive-Compulsive Disorder and Systemic Autoimmune Diseases Among Probands and Unaffected Siblings: A Nationwide Population-Based Study

ABSTRACT Objective Studies have reported a biological link between obsessive-compulsive disorder (OCD) and systemic autoimmune disease (SAID). However, whether the unaffected siblings of patients with OCD or SAID are more likely to develop subsequent SAID or OCD later in life remains unclear. Methods We examined the Taiwan National Health Insurance Research Database data of 17,135 patients with SAID, 30,672 unaffected siblings, and 467,211 non-SAID reference subjects born before 2000 for subsequent OCD during 1996–2011 and those of 25,364 patients with OCD, 42,546 unaffected siblings, and 654,207 non-OCD reference subjects to identify subsequent SAID during 1996–2011. Results Patients with SAID (odds ratio = 1.74, 95% confidence interval = 1.31–2.31) and unaffected siblings (1.25, 0.92–1.70) were more likely to develop OCD later in life than the non-SAID reference group. Moreover, patients with OCD (odds ratio = 1.53, 95% confidence interval = 1.15–2.05) and unaffected siblings (1.51, 1.21–1.87) were more likely to develop any form of SAID during the follow-up than the non-OCD reference group. Conclusions The bidirectional association of OCD and SAID between probands and siblings may indicate a familial coaggregation of these two conditions. Additional studies elucidating the genetic and environmental mechanisms underlying this coaggregation are warranted.
Age Trends in Actigraphy and Self-Report Sleep Across the Life Span: Findings From the Pittsburgh Lifespan Sleep Databank

Using individual-level cross-sectional data from the Pittsburgh Lifespan Sleep Databank, we characterized age trends and sex differences in actigraphy and self-report sleep dimensions across the healthy human life span. Our analyses revealed age trends that differed by modality and sleep dimension. Awareness of age trends in multiple sleep dimensions in healthy individuals can suggest periods of sleep-related risk or resilience and guide intervention efforts. ABSTRACT Objective Sleep changes over the human life span, and it does so across multiple dimensions. We used individual-level cross-sectional data to characterize age trends and sex differences in actigraphy and self-report sleep dimensions across the healthy human life span. Methods The Pittsburgh Lifespan Sleep Databank consists of harmonized participant-level data from sleep-related studies conducted at the University of Pittsburgh (2003–2019). We included data from 1065 (n = 577 female; 21 studies) Pittsburgh Lifespan Sleep Databank participants aged 10 to 87 years without a major psychiatric, sleep, or medical condition. All participants completed wrist actigraphy and the self-rated Pittsburgh Sleep Quality Index. Main outcomes included actigraphy and self-report sleep duration, efficiency, and onset/offset timing, and actigraphy variability in midsleep timing. Results We used generalized additive models to examine potentially nonlinear relationships between age and sleep characteristics and to examine sex differences. Actigraphy and self-report sleep onset time shifted later between ages 10 and 18 years (23:03–24:10 [actigraphy]; 21:58–23:53 [self-report]) and then earlier during the 20s (00:08–23:40 [actigraphy]; 23:50–23:34 [self-report]). Actigraphy and self-report wake-up time also shifted earlier during the mid-20s through late 30s (07:48–06:52 [actigraphy]; 07:40–06:41 [self-report]). Self-report, but not actigraphy, sleep duration declined between ages 10 and 20 years (09:09–07:35). Self-report sleep efficiency decreased over the entire life span (96.12–93.28), as did actigraphy variability (01:54–01:31). Conclusions Awareness of age trends in multiple sleep dimensions in healthy individuals—and explicating the timing and nature of sex differences in age-related change—can suggest periods of sleep-related risk or resilience and guide intervention efforts.
Ultrastructural and molecular study of the microsporidian Toguebayea baccigeri n. gen., n. sp., a hyperparasite of the digenean trematode Bacciger israelensis (Faustulidae), a parasite of Boops boops (Teleostei, Sparidae)

A new microsporidian Toguebayea baccigeri n. gen., n. sp. , hyperparasite of Bacciger israelensis (Digenea, Faustulidae), parasite of Boops boops (Teleostei, Sparidae) is described by means of transmission electron microscopy. The phylogenetic analysis, based on the SSU rDNA gene, places the new species in the clade containing mainly crustacean-infecting microsporidia of the genus Cucumispora, within superclade V (Marinosporidia) sensu Vossbrinck et al., 2014. Mature spores of T. baccigeri are ovoid, uninucleated and measure 2.5 × 1.4 μm. The number of coils of the polar tube is 8–10. The polaroplast is composed of an external lamellar part and an internal vesicular or granular part. The main differences that distinguish the new genus and new species from the closely related microsporidia include hyperparasitism in a digenean host infecting a marine fish, the geographic distribution (coast of Tunisia), presence of one nucleus at all developmental stages, disporoblastic sporogony, and the absence of sporophorous vacuoles.
Activation of osteoblast ferroptosis via the METTL3/ASK1‐p38 signaling pathway in high glucose and high fat (HGHF)‐induced diabetic bone loss

Diabetes mellitus (DM) and osteoporosis are two common diseases that may develop as a cause‐and‐effect relationship since the incidence of osteoporotic fractures is significantly increased in DM patients. However, the pathophysiology of diabetic osteoporosis is yet to be clearly understood. Iron overload has been reported to lead to bone loss and closely related to osteoporosis. In this study, we hypothesized that high glucose and high fat (HGHF) may induce osteoblastic ferroptosis for the pathogenesis of diabetic osteoporosis and explored the possible molecular mechanisms behind. Using the diabetic rat model established by HGHF feeding with a subsequent intraperitoneal injection of a single low dose of streptozocin, we found that the serum ferritin level (a biomarker for body iron store) was significantly elevated in HGHF‐fed rats and the expression of SLC7A11 and GPX4 (inhibitory marker proteins for ferroptosis) was markedly attenuated in the bone tissue of the rats with diabetic bone loss as compared to the normal rats. In an osteoblast cell model, treatment of pre‐osteoblastic MC3T3‐E1 cells with high glucose and palmitic acid (HGPA) not only suppressed osteoblast differentiation and mineralization but also triggered ferroptosis‐related osteoblastic cell death. m6A‐seq revealed that m6A methylation on ASK1 was 80.9‐fold higher in HGPA‐treated cells. The expression of p‐ASK1 and p‐p38 was also significantly elevated in the HGPA‐treated cells. Knockout of METTL3 (methyltransferase‐like 3), one of the major m6A methyltransferases, in MC3T3‐E1 cells not only abrogated HGPA‐induced activation of ASK1‐p38 signaling pathway but also attenuated the level of ferroptosis. Therefore, HGHF‐induced ferroptosis in osteoblasts may be the main cause of osteoporosis in DM via activation of METTL3/ASK1‐p38 signaling pathway, and inhibition of ferroptosis in osteoblasts may provide a potential therapeutic strategy for diabetic osteoporosis.
Attachment orientation and depression: A moderated mediation model of self-silencing and gender differences

Background: While the effect of insecure attachment on depression is well established, findings pertaining to the relationship between specific attachment dimensions (anxious and avoidant) and depression are inconsistent. The role of interpersonal factors underlying this effect has been little explored. ‘Silencing the Self’, a socio-cognitive construct may provide important insights as a mediating pathway from insecure attachment to depression and help resolve the inconsistencies. Aims: The present study explored the mediating effect of self-silencing and the role of gender as a moderator in the relation between insecure attachment orientation (i.e. avoidant and anxious) and depressive symptoms. Method: Data was collected via an online survey, from 121 adults who were in a relationship. The participants were asked to complete three self-report questionnaires, assessing attachment orientation, silencing the self and depressive symptoms. Moderated mediation analysis was performed using conditional process analysis. Results: The results indicated that the effect of both insecure attachment dimensions on depressive symptoms was mediated by silencing the self. In addition, gender moderated the association between insecure attachment and self-silencing. Conclusions: This study adds to the literature on mediating pathways between insecure attachment and depression, and provides a new perspective for therapeutic interventions in the context of depression. It indicates that professionals should focus on current social context and relational schemas of individuals with an insecure attachment, especially women, while treating cases of depression in clinical settings.
Adaptive responses to hypoxia and/or hyperoxia in humans.

SIGNIFICANCE Oxygen is indispensable for aerobic life but its utilization exposes cells and tissues to oxidative stress; thus, tight regulation of cellular, tissue and systemic oxygen concentrations is crucial. Here, we review the current understanding of how the human organism (mal-)adapts to low (hypoxia) and high (hyperoxia) oxygen levels and how these adaptations may be harnessed as therapeutic or performance enhancing strategies at the systemic level. Recent Advances: Hyperbaric oxygen therapy is already a cornerstone of modern medicine and the application of mild hypoxia, i.e., hypoxia conditioning, to strengthen the resilience of organs or the whole body to severe hypoxic insults is important preparation for high-altitude sojourns or to protect the cardiovascular system from hypoxic/ischemic damage. Many other applications of adaptations to hypo- and/or hyperoxia are only just emerging. Hypoxia conditioning - sometimes in combination with hyperoxic interventions - is gaining traction for the treatment of chronic diseases, including numerous neurological disorders, and for performance enhancement. CRITICAL ISSUES The dose- and intensity-dependent effects of varying oxygen concentrations render hypoxia- and/or hyperoxia-based interventions potentially highly beneficial, yet hazardous, although the risks vs. benefits are as yet ill-defined. FUTURE DIRECTIONS The field of low and high oxygen conditioning is expanding rapidly and novel applications are increasingly recognized, e.g., the modulation of aging processes, mood disorders or metabolic diseases. To advance hypoxia/hyperoxia conditioning to clinical applications, more research on the effects of the intensity, duration and frequency of altered oxygen concentrations, as well as on individual vulnerabilities to such interventions, is paramount.
Vibration characteristic simulation of a pneumatic artificial muscle damping seat

A type of pneumatic artificial muscle damping seat used in crawler construction vehicle is introduced. When pneumatic artificial muscle works, nonlinear problem happens. This often makes its working performance become worse. Therefore, a self-tuning fuzzy PID controller is used for pneumatic artificial muscle damping seat to decrease this influence. A simplified three degrees of freedom mathematical model of seat-vehicle body-crawler chassis is established. The vibration damping characteristics of the pneumatic artificial muscle seat are obtained using Matlab/Simulink toolbox. Under four different working conditions of crawler construction vehicle, vertical accelerations and displacements are compared between the new pneumatic artificial muscle damping seat and traditional seat. The simulation results show that the pneumatic artificial muscle seat could get better damping properties. To verify the analytical model, experiments were performed on C and G roads. The simulation results show reasonably good agreements with the experimental data. These research results could provide references for further development of pneumatic artificial muscle-type damping seat.
Redundant neural circuits regulate olfactory integration

Olfactory integration is important for survival in a natural habitat. However, how the nervous system processes signals of two odorants present simultaneously to generate a coherent behavioral response is poorly understood. Here, we characterize circuit basis for a form of olfactory integration in Caenorhabditis elegans. We find that the presence of a repulsive odorant, 2-nonanone, that signals threat strongly blocks the attraction of other odorants, such as isoamyl alcohol (IAA) or benzaldehyde, that signal food. Using a forward genetic screen, we found that genes known to regulate the structure and function of sensory neurons, osm-5 and osm-1, played a critical role in the integration process. Loss of these genes mildly reduces the response to the repellent 2-nonanone and disrupts the integration effect. Restoring the function of OSM-5 in either AWB or ASH, two sensory neurons known to mediate 2-nonanone-evoked avoidance, is sufficient to rescue. Sensory neurons AWB and downstream interneurons AVA, AIB, RIM that play critical roles in olfactory sensorimotor response are able to process signals generated by 2-nonanone or IAA or the mixture of the two odorants and contribute to the integration. Thus, our results identify redundant neural circuits that regulate the robust effect of a repulsive odorant to block responses to attractive odorants and uncover the neuronal and cellular basis for this complex olfactory task.
Trackmate : large-scale accessibility of Tangible User Interfaces

There is a long history of Tangible User Interfaces (TUI) in the community of humancomputer interaction, but surprisingly few of these interfaces have made it beyond lab and gallery spaces. This thesis explores how the research community may begin to remedy the disconnect between modern TUIs and the everyday computing experience via the creation and dissemination of Trackmate, an accessible (both ubiquitous and enabling) tabletop tangible user interface that scales to a large number of users with minimal hardware and configuration overhead. Trackmate is entirely open source and designed: to be community-centric; to leverage common objects and infrastructure; to provide a low floor, high ceiling, and wide walls for development; to allow user modifications and improvisation; to be shared easily via the web; and to work alongside a broad range of existing applications and new research interface prototypes. Thesis Supervisor: Hiroshi Ishii Title: Muriel R. Cooper Professor of Media Arts and Sciences
PATENTS AND PHARMACEUTICALS IN THE UK: AN INSIGHT INTO THE PATENTING PROCESS

The purpose of this paper is to present some findings of how UK pharmaceutical firms use the patenting process to help in getting excludability in the marketplace, and why those firms file patent applications. A qualitative approach was used to investigate that topic. In particular, we run semi-structured interviews with the personnel who head the decision-making process concerned with patents. A common response on why firms engage in the patenting process was the long development time of a new product, and the costs associated with that. As patents help in keeping imitators apart those who come up with new technical knowledge are more likely to recoup the investments in R&D. Excludability is also sought by patenting, in the major markets, several embodiments of the invention in the form of either a single patent or a series of patents, and by patenting complementary technologies that come out along the R&D process.
Role of anterior midcingulate cortex in self‐reward representation and reward allocation judgments within social context

Evaluating rewards for the self and others is essential for social interactions. Previous research has probed the neural substrates signaling rewards in social decision‐making tasks as well as the differentiation between self‐ and other‐reward representations. However, studies with different designs have yielded mixed results. After analyzing and comparing previous designs, we differentiated three components in this study: task (reward representation vs. social judgment of reward allocation), agency (self vs. other), and social context (without vs. within). Participants were asked to imagine various share sizes as a proposer in a dictator game during fMRI, and then rated their willingness and preference for these offers in a post‐scan behavioral task. To differentiate the regions involved in processing rewards without and within context, we presented the reward to each agent in two sequential frames. Parametric analyses showed that, in the second frame (i.e., within social context), the anterior midcingulate cortex (aMCC) signaled self‐reward and preferences for the offer, whereas the right insula tracked the likelihood of proposing the offer. Belief in a just world is positively associated with aMCC responses to self‐reward. These results shed light on the role of the aMCC in coding self‐reward within the social context to guide social behaviors.
Learning representations with information on hand

Representation (e.g. feature or kernel) of samples is crucial for machine learning algorithms. Usually, the raw representation is not good enough to provide satisfactory performance. Hence, it is necessary to learn new and/or better representations for samples collected from different sources. In this thesis, three new methods for learning effective representation from multiple kernels, from auxiliary datasets and from the difference between domains respectively are proposed. The first one is on learning kernel from candidate kernels. Most dimensionality reduction techniques are based on one metric or one kernel, hence it is necessary to select an appropriate kernel for kernel-based dimensionality reduction. Multiple kernel learning for dimensionality reduction (MKL-DR) has been recently proposed to learn a kernel from a set of base kernels which are seen as different descriptions of data. As MKL-DR does not involve regularization, it might be ill-posed under some conditions and consequently its applications are hindered. As such, a multiple kernel learning framework for dimensionality reduction based on regularized trace ratio, termed as MKL-TR, is developed. Our method aims at learning a transformation into a space of lower dimension and a corresponding kernel from the given base kernels among which some may not be suitable for the given data. The solutions for the proposed framework can be found based on trace ratio maximization. The experimental results demonstrate its effectiveness in benchmark datasets, which include text, image and sound datasets, for supervised, unsupervised as well as semi-