Miracle-dz/UniFAR-FTUs huggingface dataset:
Niclosamide targets macrophages to rescue the disrupted peritoneal homeostasis in endometriosis

Due to the vital roles of macrophages in the pathogenesis of endometriosis, targeting macrophages could be a new therapeutic direction. Here, we investigated the efficacy of niclosamide for the resolution of perturbed microenvironment caused by dysregulated macrophages in a mouse model of endometriosis. Single-cell transcriptomic analysis revealed the heterogeneity of macrophage subpopulations including three newly identified intermediate subtypes with sharing characteristics of traditional “small” or “large” peritoneal macrophages (SPMs and LPMs) in the peritoneal cavity. Endometriosis-like lesions (ELL) enhanced the differentiation of recruited macrophages, promoted the replenishment of resident LPMs, and increased ablation of embryo-derived LPMs, which were stepwise suppressed by niclosamide. In addition, niclosamide reversed intercellular communications between macrophages and B cells which were disrupted by ELL. Therefore, niclosamide rescued the perturbed microenvironment in endometriosis through its fine regulations on the dynamic progression of macrophages and could be a new promising therapy for endometriosis. Summary Niclosamide tunes the dynamic progression of peritoneal macrophages and their intercellular communications with B cells to rescue the disrupted microenvironment in the peritoneal cavity in a mouse model of endometriosis. Graphic Abstract
The theta paradox: 4-8 Hz EEG oscillations reflect both local sleep and cognitive control

Human brain activity generates electroencephalographic (EEG) oscillations that characterize specific behavioral and vigilance states. The frequency of these oscillations is typically sufficient to distinguish a given state, however theta oscillations (4-8 Hz) have instead been found in near-opposite conditions of drowsiness during sleep deprivation and alert cognitive control. While the latter has been extensively studied and is often referred to as “frontal midline theta”, the former has been investigated far less but is considered to be a marker for local sleep during wake. In this study we investigated to what extent theta oscillations differed during cognitive tasks and sleep deprivation. We measured high-density EEG in 18 young healthy adults performing 6 tasks under 3 levels of sleep deprivation. We found both cognitive load and sleep deprivation increased theta power in medial prefrontal cortical areas, however sleep deprivation caused additional increases in theta in many other, predominantly frontal, areas. The sources of sleep deprivation theta were task-dependent, with a visual-spatial task and short-term memory task showing the most widespread effects. Notably, theta was highest in supplementary motor areas during passive music listening, and highest in the inferior temporal cortex during a spatial game. This suggests that theta caused by sleep deprivation may preferentially occur in cortical areas not involved in ongoing behavior. While our results find differences in topography from frontal midline theta, they raise the possibility that a common mechanism may underly both theta oscillations during cognition and during sleep deprivation.
Concentration dependent dual effect of the endozepine ODN on neuronal spiking activity

Endozepines, known as the endogenous ligands of benzodiazepine-binding sites, include the diazepam binding inhibitor (DBI) and its processing products, the triakontatetraneuropeptide (TTN) and the octadecaneuropeptide (ODN). Despite indisputable evidences of the binding of ODN on GABAAR-BZ-binding sites, their action on this receptor lacks compelling electrophysiological observations, some studies reporting that ODN acts as a negative allosteric modulator (NAM) of GABAAR while others suggest the opposite (positive allosteric modulation, PAM effect). All these studies were carried out in vitro with various neuronal cell types. To further elucidate the role of ODN on neuronal excitability, we tested its effect in vivo in the cortex of the anesthetized mouse. Spontaneous neuronal spikes were recorded by the mean of an extracellular pipette in the vicinity of which ODN was micro-infused, either at high dose (10-5M) or low dose (10-11M). ODN at high dose induced a significant increase of neuronal spiking. This effect could be antagonized by the GABAAR-BZ-binding sites blocker flumazenil. In sharp contrast, at low concentration, ODN reduced neuronal spiking in a magnitude similar to GABA itself. Interestingly, this decrease of neuronal activity by low dose of ODN was not flumazenil dependent suggesting that this effect is mediated by another receptor. Finally, we show that astrocytes in culture, known to be stimulated by picomolar dose of ODN via a GPCR, increased their export of GABA when stimulated by low dose of ODN. Our results confirm the versatility of ODN in the control of GABA transmission, but suggest that its PAM-like effect is, at least in part, mediated via an astrocytic non-GABAAR ODN receptor.
Genotypic sex shapes maternal care in the African Pygmy mouse, Mus minutoides

Sexually dimorphic behaviours, such as parental care, have long been thought to be driven mostly, if not exclusively, by gonadal hormones. In the past two decades, a few studies have challenged this view, highlighting the direct influence of the sex chromosome complement (XX vs XY or ZZ vs ZW). The African pygmy mouse, Mus minutoides, is a wild mouse species with naturally occurring XY sex reversal induced by a third, feminizing X* chromosome, leading to three female genotypes: XX, XX* and X*Y. Here, we show that sex reversal in X*Y females shapes a divergent maternal care strategy from both XX and XX* females, rather than altering care quality. In addition, we show that sex reversal may also impact the dopaminergic system in the anteroventral periventricular nucleus of the hypothalamus, consistent with one component of maternal care: pup retrieval. Combining behavioural ecology and neurobiology in a rodent subject to natural selection, we evaluate potential candidates for the neural basis of maternal behaviours and strengthen the underestimated role of the sex chromosomes in shaping sex differences in brain and behaviours. All things considered, we further highlight the emergence of a third sexual phenotype, challenging the binary view of phenotypic sexes.
The gene knockout of angiotensin II type 1a receptor improves high-fat diet-induced obesity in rat via promoting adipose lipolysis

Aims The renin-angiotensin system (RAS) is over-activated and the serum angiotensin II (Ang II) level increased in obese patients, while their correlations were incompletely understood. This study aims to explore the role of Ang II in diet-induced obesity by focusing on adipose lipolysis. Methods Rat model of AT1aR gene knockout were established to investigate the special role of Ang II. Wild-type (WT) and AT1aR gene knockout (AT1aR-/-) SD rats were fed with normal diet or high-fat diet for 12 weeks. Adipose morphology and adipose lipolysis were examined. Results AT1aR deficiency activated lipolysis-related enzymes and increased the levels of NEFAs and glycerol released from adipose tissue in high-fat diet rats, while did not affect triglycerides synthesis. Besides, AT1aR knockout promoted energy expenditure and fatty acids oxidation in adipose tissue. cAMP levels and PKA phosphorylation in the adipose tissue were significantly increased in AT1aR-/- rats fed with high-fat. Activated PKA could promote adipose lipolysis and thus improved adipose histomorphology and insulin sensitivity in high-fat diet rats. Conclusions AT1aR deficiency alleviated adipocyte hypertrophy in high-fat diet rats by promoting adipose lipolysis via cAMP/PKA pathway, and thereby delayed the onset of obesity and related metabolic diseases.
Pharmacological inhibition of titan-like cells formation suggests that accumulation of endogenous free radicals that correlate with mitochondrial changes are required to induce this transition in Cryptococcus neoformans

Cryptococcus neoformans is an encapsulated yeast able to cause disease (mainly meningoencephalitis) among immunosuppressed patients, mostly HIV+. This yeast can form the so-called titan cells in vivo, which are cells of an abnormal larger size due to an increase in both the capsule and the cell body size (total size reaching between 50-70 microns). This phenomenon can be partially reproduced in vitro to obtain cells of an intermediate size (25-30 um), which have been denominated titan-like cells. In this work, we have screened 1,520 compounds from the Prestwick Chemical Library and identified off-patent drugs that inhibited titan-like cell formation in vitro. We developed an automated fluorescence-based microscopy assay and identified 64 compounds as possible inhibitors of titan-like cells in vitro. We chose 10 of these compounds to confirm their inhibitory effect and confirmed them as inhibitors of titan-like cells with dose-response curves. Several of the compounds identified had antioxidant properties (i.e., retinoic acid), indicating a possible role of free radicals during titan cell formation. Using fluorescent probes, we found that there was an endogenous accumulation of ROS during cell growth, which was inhibited in the presence of retinoic acid. Furthermore, we found that during titanization, there were significant changes in the mitochondria, which is the main organelle where ROS are produced. We hypothesize that an intracellular increase of free radicals at the mitochondria might be a triggering signal to induce titanization. Importance Cryptococcus neoformans is an excellent model to investigate fungal pathogenesis. This yeast can produce “titan cells”, which are cells of an abnormal larger size that contribute to the persistence of the yeast in the host. In this work, we have used a new approach to characterize them, which is identifying drugs that inhibit this process. We have used a repurposing off- patent drug library, combined with an automatic method to image and analyse fungal cell size. In this way, we have identified many compounds that inhibit this transition. Interestingly, several compounds were antioxidants, allowing us to confirm that endogenous ROS and mitochondrial changes are important for titan cell formation. This work provides new evidences of the mechanisms required for titanization. Furthermore, the future characterization of the inhibitory mechanisms of the identified compounds by the scientific community will contribute to better understand the role of titan cells in virulence.
Analysis of non-human primate models for evaluating prion disease therapeutic efficacy

Prion disease is a fatal neurodegenerative disease caused by the conformational corruption of the prion protein (PrP), encoded by the prion protein gene (PRNP). While no disease-modifying therapy is currently available, genetic and pharmacological proofs of concept support development of therapies that lower PrP levels in the brain. In light of proposals for clinical testing of such drugs in presymptomatic individuals at risk for genetic prion disease, extensive nonclinical data are likely to be required, with extra attention paid to choice of animal models. Uniquely, the entire prion disease process can be faithfully modeled through transmission of human prions to non-human primates (NHPs), raising the question of whether NHP models should be used to assess therapeutic efficacy. Here we systematically aggregate data from N=527 prion-inoculated animals spanning six decades of research studies. Using this dataset, we assess prion strain, route of administration, endpoint, and passage number to characterize the relationship of tested models to currently prevalent human subtypes of prion disease. We analyze the incubation times observed across diverse models and perform power calculations to assess the practicability of testing prion disease therapeutic efficacy in NHPs. We find that while some models may theoretically be able to support therapeutic efficacy studies, pilot studies would be required to confirm incubation time and attack rate before pivotal studies could be designed, cumulatively requiring several years. The models with the shortest and most tightly distributed incubation times are those with smaller brains and weaker homology to humans. Our findings indicate that it would be challenging to conduct efficacy studies in NHPs in a paradigm that honors the potential advantages of NHPs over other available models, on a timeframe that would not risk unduly delaying patient access to promising drug candidates.
PERFORMANCE ANALYSIS OF SELECTION COOPERATION SYSTEM WITH DYNAMICALLY CHANGING RELAY NUMBER

Selection cooperation has been widely investigated as a simple but eﬃcient strategy to improve the performance of cooperative systems. In the most of previous works, the analysis of selection cooperation has largely focused on the assumption that the number of available relays is deterministic. However, in many practical systems, one relay may be occupied by other users and thus it is unavailable for a special user (i.e., the given source) in one transmission, which will cause a change in the number of available relays for the special user. As a result, the previous analysis may not be valid in this case. In this paper, we analyze the outage performance of decode-and-forward (DF) selection cooperation system with dynamically changing relay number (DC-RN). By modeling each relay service for the given source in this proposed system as a Markov on-oﬀ chain, a close-form expression for outage probability is derived. Our numerical results verify the accuracy of the obtained analytical results.
Continuation of a physical model of brass instrument: application to trumpet categorization

The system formed by the couple { player - trumpet } falls into the class of non-linear dynamical systems likely to be studied using diﬀerent numerical tools such as numerical continuation methods. In this study we illustrate the interest of this approach for the categorization of Bb trumpets in the space of some performance descriptors obtained from continuation by the ANM method combined to the Harmonic Balance Method (HBM). The model considered is based on one-dimensional lip model, coupled to the resonator impedance described by a series of complex modes similar to what proposed in [1]. The coupling between the mechanical oscillator and the acoustic resonator is achieved by a Bernoulli ﬂow equation, considering turbulent mixing in the mouthpiece with no pressure recovery [2]. The mechanical and acoustic equations are given in system 1, where y is the vertical lip position ( y 0 is the lip position at rest), ω l , Q l , µ l and b the mechanical lip parameters, s k and C k with k ∈ [1 , N ] the modal parameters of the N resonances of the acoustic impedance of the instrument, Z c the characteristic impedance, u the volume ﬂow, p the downstream pressure at the input of the instrument (in the mouthpiece), and p 0 the upstream (mouth) static pressure.
Best friends forever and family ties: continuity and change in closeness with parents and friends among Australian adolescents

ABSTRACT During adolescence, the need for social connection increases. Yet, fostering emotional closeness in relationships becomes more complex, as the need for autonomy also increases and social environments must adapt to become conducive to these seemingly competing needs. This complexity necessitates more research on what happens to close relationships during adolescence to better equip parents, scholars, and practitioners are in helping individuals navigate the unique social atmosphere of adolescence. The current study draws upon multi-level modelling techniques to estimate growth models of Australian adolescents’ closeness to parents and closeness to friends from ages 12–17 as well as explore predictors of these trajectories. Findings reveal that on average, adolescents’ levels of closeness to parents exhibit a moderate decrease while remaining relatively high, and boys appear to have a closer relationship with their parents than girls throughout the period examined. Levels of closeness to friends similarly decline while remaining relatively high, with girls exhibiting both greater levels of closeness and a faster decrease than boys throughout the timeframe examined. These results are discussed in light of the current literature, and recommendations for future studies are provided.
An enhanced course in digital communications

Today technological improvements provide several alternatives and opportunities for improving traditional educational systems.However, integrating these technologies in an appropriate and successful way into the curriculum of traditional systems is achallenge. This work presents the enhancements added to an undergraduate course on Digital Communications which is anintroductory course offered to senior undergraduates or first year graduate students. The Digital Communications course coverssome essential stages in a typical digital communication system, namely, signal formatting such as analog to digital conversion,baseband modulation and bandpass modulation by concentrating on demodulation and detection at the receiver end. Theenhancements include computer simulations, web-based simulation tools and remote laboratory experiments along with several outof class activities. The enhancements have improved the course significantly by supporting constructivist and blended learningmethods. The improvement to the course was demonstrated over two years, from the student progress assessed from the collatedresults of the student evaluation forms and a questionnaire on the course learning outcomes, and a comparison of theirperformance in the written exams. The results show that there is a significant improvement both in the progress and satisfaction ofthe students on the enhanced course curriculum. This study shows how different technologies have been successfully integrated tothe curriculum of Digital Communications course in a higher education organization and concludes its success factors.
Switching of Redox Signaling by Prdx6 Expression Decides Cellular Fate by Hormetic Phenomena Involving Nrf2 and Reactive Oxygen Species

Changes in intracellular reactive oxygen species (ROS) levels due to remodeling of antioxidant defense can affect the status of biological homeostasis in aging/oxidative stress. Peroxiredoxin 6 (Prdx6), an antioxidant gene downstream target for the Nrf2 pathway, plays a role in regulating ROS homeostasis. Using aging human (h) lens epithelial cells (LECs) or Prdx6-deficient (Prdx6−/−) mouse (m) LECs, here we showed that dichlorofluorescein (DCF) oxidation or H2O2 were strictly controlled by Prdx6. We observed that a moderate degree of oxidative stress augmented Nrf2-mediated Prdx6 expression, while higher doses of H2O2 (≥100 µM) caused a dramatic loss of Prdx6 expression, resulting in increased DCF oxidation and H2O2 amplification and cell death. Mechanistically, at increased oxidative stress, Nrf2 upregulated transcriptional factor Klf9, and that Klf9 bound to the promoter and repressed the Prdx6 gene. Similarly, cells overexpressing Klf9 displayed Klf9-dependent Prdx6 suppression and DCF oxidation with H2O2 amplification, while ShKlf9 reversed the process. Our data revealed that H2O2 and DCF oxidation levels play a hormetical role, and the Nrf2-Klf9-Prdx6 pathway is pivotal for the phenomena under the conditions of oxidative load/aging. On the whole, the results demonstrate that oxidative hormetical response is essentially based on levels of oxidative triggering and the status of Klf9-Prdx6 pathway activation; thus, Klf9 can be considered as a therapeutic target for hormetic shifting of cellular defense to improve protective resilience to oxidative stress.
Adaptive Formation Control of Unmanned Underwater Vehicles with Collision Avoidance under Unknown Disturbances

In this paper, the formation control problem for a group of unmanned underwater vehicles (UUVs) is investigated considering collision avoidance and environment disturbances. To address the external force effect of the environment, such as waves and currents, a sliding mode disturbance observer is designed to compensate for the unknown dynamic disturbances in finite time. A bounded artificial potential field is incorporated into the control law to ensure collision avoidance among UUVs. The form of an artificial potential function is much simpler and convenient for engineering applications. A controller is devised to guarantee all the error signals are bounded, and the formation pattern can be achieved in finite time after collision avoidance. The stability of UUV formation with collision avoidance is proven by using the Lyapunov theorem, and the scheme has been shown to be convergent using Barbalat’s lemma. Comparative simulations are presented to demonstrate the effectiveness of the proposed method in 2-D and 3-D environments.
Structural and Mechanical Properties of Fluorine-Containing TaCxNy Thin Films Deposited by Reactive Magnetron Sputtering

TaN thin-film coatings are well known for their good mechanical properties, acceptable toughness, as well as good biocompatibility. However, the friction coefficient of these films is sometimes too high, or the hemocompatibility is poor. The purpose of this study is to reduce the friction coefficient and increase the hydrophobicity of TaN coatings by introducing carbon and fluorine into the coatings. This study has never been conducted by other researchers. Fluorine-containing tantalum carbonitride (i.e., F–TaCxNy) top layers were deposited on TaN/Ta interlayers by reactive sputtering with fixed nitrogen and various hexafluoroethane (C2F6) mass flow rates. During the deposition process, C2F6 gas with various mass flow rates was added. After deposition, these F–TaCxNy multi-layered films were then characterized using XRD, XPS, FTIR, FESEM, WDS, a nano-indenter, a water contact-angle measurement system, and a tribometer. The tribological tests were carried out in the environment with and without humidity. The surface energies of the films were examined with water contact-angle variation. According to structural analysis, TaN phase would transform to TaCxNy with the increase in the C2F6 mass flow rate, which would result in a decrease in the friction coefficient and an increase in hydrophobicity. The films’ hardness (H, increased at most by 20%), elastic modulus (E), and H/E ratio first increased then decreased, most likely due to the increase in relatively soft C–F bonding. According to the results obtained from tribotesting, it was found that an increase in carbon and fluorine contents in the films reduces the friction by more than 30%, and wear rate by more than 50%. More importantly, the effects of moisture on the friction coefficient can be minimized to almost nothing. In a water contact-angle study, the contact angle increased from 60° to 85° with the increase in C2F6 mass flow rates. This evidence illustrated that hemocompatibility of the TaN thin film can be significantly enhanced through the formation of Ta–C and C–Fx bonding. The chemical composition and bonding status of these films, especially the existence of C–Fx bonds, were studied by FTIR and XPS. In sum, with the increased C2F6 mass flow rate, the carbon and fluorine contents in the films increased, while the nitrogen content decreased. The structure, bonding status, and compositions varied accordingly. The tribological behaviors were significantly improved. Furthermore, by carrying out tribotesting in humid air and a dry argon environment, it was confirmed that the greater the fluorine content, the less sensitive the films would be to environment change. This is attributable to the induced lower surface energy and reduced adsorption to water vapor due to the increase in C–Fx bonds. The successfully fabricated and studied F–TaCxNy films could be applied in many areas such as artificial blood vessels, or precision components in an atmospheric or vacuum environment.