Miracle-dz/UniFAR-FTUs huggingface dataset:
Differential mechanisms of desensitization of 5‐HT1A receptors in the dorsal raphe nucleus (DRN) following chronic treatment with selective serotonin reuptake inhibitors (SSRIs)

There is generally a two‐three week delay in obtaining therapeutic effectiveness with antidepressants, which has been attributed to compensatory changes in neurotransmitter systems. One example is the desensitization of somatodendritic 5‐HT1A autoreceptors in the DRN following chronic SSRI administration. Treatment of rats for 14 days with the SSRI fluoxetine (10 mg/kg, i.p.) results in a decrease in the efficacy of the 5‐HT1A receptor agonist 8‐OH‐DPAT to stimulate [35S]GTPγS binding in the DRN [Emax (%above basal): saline‐treated = 44 ± 5.5; fluoxetine‐treated = 31.1 ± 4.4]. In contrast, chronic administration of the SSRIs citalopram (18 mg/kg/day, 14 days) or sertraline (10 mg/kg/day, 21 days) via osmotic minipump did not result in changes in the efficacy or potency of 8‐OH‐DPAT to stimulate [35S]GTPγS binding. The binding of [3H]8‐OH‐DPAT to the coupled, high‐affinity agonist state of the receptor was unaltered by these treatments. Thus, not all SSRIs when administered chronically decrease the capacity of 5‐HT1A receptors to activate G‐proteins in the DRN. We hypothesize that the mechanism by which chronic fluoxetine administration decreases the capacity of 5‐HT1A receptors to activate G‐proteins in the DRN is due to phosphorylation of G proteins. Because fluoxetine has moderate affinity for the norepinephrine transporter (Kd=119–473nM), we propose that chronic fluoxetine treatment may result in activation of alpha‐1 noradrenergic receptors in the DRN. Phosphorylation of Gα by PKC inhibits signal transduction via Gαi, to which 5‐HT1A receptors are coupled.
Promoting the Efficiency and Stability of CsPbIBr2-Based All-Inorganic Perovskite Solar Cells through a Functional Cu2+ Doping Strategy.

Although organic-inorganic halide perovskite solar cells (PSCs) have shown dramatically enhanced power conversion efficiencies (PCEs) in the last decade, their long-term stability is still a critical challenge for commercialization. To address this issue, tremendous research efforts have been devoted to exploring all-inorganic PSCs because of their intrinsically high structural stability. Among them, CsPbIBr2-based all-inorganic PSCs have drawn increasing attention owing to their suitable bandgap and favourable stability. However, the PCEs of CsPbIBr2-based PSCs are still far from those of their organic-inorganic counterparts, thus inhibiting their practical applications. Herein, we demonstrate that by simply doping an appropriate amount of Cu2+ into a CsPbIBr2 perovskite lattice (0.5 at.% to Pb2+), the perovskite crystallinity and grain size are increased, the perovskite film morphology is improved, the energy level alignment is optimized and the trap density and charge recombination are reduced. As a consequence, a decent PCE improvement from 7.81% to 10.4% is achieved along with an enhancement ratio of 33% with a CsPbIBr2-based PSC. Furthermore, the long-term stability of CsPbIBr2-based PSCs against moisture and heat is also remarkably improved by Cu2+ doping. This work provides a facile and effective route to improve the PCE and long-term stability of CsPbIBr2-based all-inorganic PSCs.
Beneficial Effects of Melatonin in the Ovarian Transport Medium on In Vitro Embryo Production of Iberian Red Deer (Cervus elaphus hispanicus)

Simple Summary The development of in vitro embryo production (IVP) in wild species, such as Iberian red deer, can become a daunting challenge since prolonged ovary transport times to the laboratory are often unavoidable. This may have detrimental effects on the quality and developmental capacity of oocytes. We evaluated the effect of supplementing the ovary transport medium with the antioxidant melatonin and observed an increased level of oocyte intracellular reduced glutathione content. Moreover, melatonin enhanced cleavage and blastocyst rates and had a positive effect on embryo quality in terms of the expression of essential embryo development-related genes. In conclusion, the addition of melatonin to the ovary storage medium could mitigate the negative impacts that long transport times may have on oocyte developmental competence and quality of the resulting blastocysts in Iberian red deer. Abstract A major limiting factor for the development of in vitro embryo production (IVP) in wild species, such as Iberian red deer, compared to livestock animals is the poor availability and limited access to biological material. Thus, the use of post-mortem ovaries from slaughtered animals represent a source of oocytes for the large scale production of embryos needed for research and to improve the efficiency of IVP. However, these oocytes are not as developmentally competent as their in vivo counterparts. Moreover, oocytes are usually obtained from ovaries that have been transported for long distances, which may also affect their quality. In order to overcome the issues associated with prolonged storage times of post-mortem material, in this study we examined the effect of melatonin supplementation to the ovary transport medium on oocyte quality, embryo yield, and blastocyst quality in Iberian red deer. When necessary, sheep was used as an experimental model due to the large number of samples required for analysis of oocyte quality parameters. Oocytes were in vitro matured and assessed for early apoptosis; DNA fragmentation; reactive oxygen species (ROS); reduced glutathione (GSH) content, mitochondrial membrane potential, and distribution; and relative abundance of mRNA transcript levels. After in vitro fertilization, embryo rates and blastocyst quality were also investigated. The results revealed that melatonin treatment significantly increased intracellular level of GSH in sheep oocytes. Moreover, the percentage of cleavage and blastocyst yield in red deer was greater compared to the Control group and there was lower abundance of oxidative stress- and apoptosis-related SHC1, TP53, and AKR1B1 mRNA transcripts in blastocysts for the Melatonin group. In conclusion, the supplementation of melatonin to the ovary storage medium had a positive effect on the developmental competence and quality of resulting blastocysts in Iberian red deer.
Derivatives of usnic acid cause cytostatic effect in Caco-2 cells

Abstract Usnic acid has anti-cancer activity, however, low solubility and toxicity limit the potential. To investigate biological activity of usnic acid derivatives, enantiopure derivatives were synthesised by reacting usnic acid with ethylenediamine, which yielded one dimer product ((+)-1), and two tetra cyclic compounds ((+)-2 and (-)-2). The products were characterised with NMR, and evaluated in vitro in human colon cancer cell line Caco-2 by cell count, phase-contrast microscopy, MTT-assay, measurement of DNA content and cell cycle distribution. All compounds tested showed cytostatic effect in Caco-2 cells, but each compound had a distinct cellular effect. Compound (+)-1 showed anti-proliferative activity by increasing the percentage of cells in S-phase with 25% compared to the control. Compounds (+)-2 and (-)-2 induced paraptosis, but only compound (+)-2 modulated cell cycle distribution by accumulating cells in G2/M-phase by 47% and reduced DNA content by 60%. All compounds express interesting cellular and potential anti-proliferative activity. Graphical Abstract
Gene Expression Control by Chromatin Binding Factors

textabstractIn nature, the hereditary material that contains the instructions for making all living matter is known as deoxyribonucleic acid (DNA). Almost all the cells in our body, except mature red blood cells, have DNA of which the vast majority is located in the nucleus. DNA is composed of long stretches of nucleotides, which themselves are build up of sugar (deoxyribose), phosphate, and two kinds of nucleobases, i.e. purines and pyrimidines. The purine bases comprise adenine (A) and guanine (G), whereas the pyrimidines consist of cytosine (C) and thymine (T). In general, DNA is formed by two nucleotide strands which together assemble into a double helix structure (Watson and Crick, 1953). Within this double-stranded helix, the nucleobases present in opposite strands form hydrogen bonds with each other in such a way that adenine forms base pairs with thymine (A-T) and cytosine pairs up with guanine (C-G). As a consequence of this base pairing, the nucleobases adenine and thymine and cytosine and guanine are present in approximately equal amounts, with A and T each accounting for roughly 30%, whereas C and G each make up 20% of the four bases in human (Chargaff et al., 1950). The relative amounts of A, G, C, and T and, therefore, the composition of DNA vary from one species to another though. The DNA can be divided into several functional domains, such as genic and non-genic regions. The genic regions contain genes, which are pieces of DNA encoding either protein or non-coding ribonucleic acid (ncRNA). In case of the protein-coding genes, information embedded within these genes is transmitted by an intermediate molecule, the messenger RNA (mRNA). This occurs through a process called transcription, which will be explained in more detail later on. The non-genic regions often fulfill regulatory functions which are important for gene transcription.
Incidence of Uveitis in Secukinumab‐treated Patients With Ankylosing Spondylitis: Pooled Data Analysis From Three Phase 3 Studies

The objective of this study was to report the incidence of uveitis in secukinumab‐treated patients with ankylosing spondylitis (AS) in a pooled analysis of three phase 3 trials (MEASURE 1‐3 [ClinicalTrials.gov identifiers NCT01358175, NCT01649375, NCT02008916]).
Clinical Evidence for Q10 Coenzyme Supplementation in Heart Failure: From Energetics to Functional Improvement

Oxidative stress and mitochondrial dysfunction are hallmarks of heart failure (HF). Coenzyme Q10 (CoQ10) is a vitamin-like organic compound widely expressed in humans as ubiquinol (reduced form) and ubiquinone (oxidized form). CoQ10 plays a key role in electron transport in oxidative phosphorylation of mitochondria. CoQ10 acts as a potent antioxidant, membrane stabilizer and cofactor in the production of adenosine triphosphate by oxidative phosphorylation, inhibiting the oxidation of proteins and DNA. Patients with HF showed CoQ10 deficiency; therefore, a number of clinical trials investigating the effects of CoQ10 supplementation in HF have been conducted. CoQ10 supplementation may confer potential prognostic advantages in HF patients with no adverse hemodynamic profile or safety issues. The latest evidence on the clinical effects of CoQ10 supplementation in HF was reviewed.
Differences in HIV Markers between Infected Individuals Treated with Different ART Regimens: Implications for the Persistence of Viral Reservoirs

In adherent individuals, antiretroviral therapy (ART) suppresses HIV replication, restores immune function, and prevents the development of AIDS. However, ART is not curative and has to be followed lifelong. Persistence of viral reservoirs forms the major obstacle to an HIV cure. HIV latent reservoirs persist primarily by cell longevity and proliferation, but replenishment by residual virus replication despite ART has been proposed as another potential mechanism of HIV persistence. It is a matter of debate whether different ART regimens are equally potent in suppressing HIV replication. Here, we summarized the current knowledge on the role of ART regimens in HIV persistence, focusing on differences in residual plasma viremia and other virological markers of the HIV reservoir between infected individuals treated with combination ART composed of different antiretroviral drug classes.
Multifaceted role of glycosylation in transfusion medicine, platelets, and red blood cells

Glycosylation is highly prevalent, and also one of the most complex and varied posttranslational modifications. This large glycan diversity results in a wide range of biological functions. Functional diversity includes protein degradation, protein clearance, cell trafficking, cell signaling, host‐pathogen interactions, and immune defense, including both innate and acquired immunity. Glycan‐based ABO(H) antigens are critical in providing compatible products in the setting of transfusion and organ transplantation. However, evidence also suggests that ABO expression may influence cardiovascular disease, thrombosis, and hemostasis disorders, including alterations in platelet function and von Willebrand factor blood levels. Glycans also regulate immune and hemostasis function beyond ABO(H) antigens. Mutations in glycogenes (PIGA, COSMC) lead to serious blood disorders, including Tn syndrome associated with hyperagglutination, hemolysis, and thrombocytopenia. Alterations in genes responsible for sialic acids (Sia) synthesis (GNE) and UDP‐galactose (GALE) and lactosamine (LacNAc) (B4GALT1) profoundly affect circulating platelet counts. Desialylation (removal of Sia) is affected by human and pathogenic neuraminidases. This review addresses the role of glycans in transfusion medicine, hemostasis and thrombosis, and red blood cell and platelet survival.
Acetylcholinesterase electrochemical biosensors with graphene-transition metal carbides nanocomposites modified for detection of organophosphate pesticides

An acetylcholinesterase biosensor modified with graphene and transition metal carbides was prepared to detect organophosphorus pesticides. Cyclic voltammetry, differential pulse voltammetry, and electrochemical impedance spectroscopy were used to characterize the electrochemical catalysis of the biosensor: acetylcholinesterase/chitosan-transition metal carbides/graphene/glassy carbon electrode. With the joint modification of graphene and transition metal carbides, the biosensor has a good performance in detecting dichlorvos with a linear relationship from 11.31 μM to 22.6 nM and the limit of detection was 14.45 nM. Under the premise of parameter optimization, the biosensor showed a good catalytic performance for acetylcholine. Compared to the biosensors without modification, it expressed a better catalytic performance due to the excellent electrical properties, biocompatibility and high specific surface area of graphene, transition metal carbides. Finally, the biosensor exhibits good stability, which can be stored at room temperature for one month without significant performance degradation, and has practical potential for sample testing.
Resemblance within flocks and individual differences in feather mite abundance on long-tailed tits, Aegithalos caudatus (L.)

Abstract Even though feather mites are arthropod ectosymbionts widely distributed on almost all orders of birds, the nature and functional relationship of the interaction between feather mites and birds remain unclear. In this paper, we analyzed factors determining the distribution of feather mites at the individual as well as at the flock level, searching for correlates with bird characteristics such as body size and fat accumulation during winter. Long-tailed tits, Aegithalos caudatus (L.), live in family flocks during winter. Foraging, roosting and territory defence are done in groups. Communal roosting facilitates direct body contact among flock members, which may enhance the transmission of feather mites. Feather mite abundance was more similar within than among flocks. Within flocks, those individuals with longer wings and better body condition as determined by fat scores had larger numbers of feather mites. At the flock level, no relationship was found between mean mite intensity and any of the considered variables. We show that the distribution of feather mites among long-tailed tits is not random, but is shaped by individual features and flock ownership.
Pyropia Yezoensis Extract Suppresses IFN-Gamma- and TNF-Alpha-Induced Proinflammatory Chemokine Production in HaCaT Cells via the Down-Regulation of NF-κB

Pyropia yezoensis, a red alga, is popular and harvested a lot in East Asia and is famous for its medicinal properties attributable to its bioactive compounds including amino acids (porphyra-334 and shinorine, etc.), polysaccharides, phytosterols, and pigments, but its anti-inflammatory effect and mechanism of anti-atopic dermatitis (AD) have not been elucidated. In this study, we investigate the anti-AD effect of P. yezoensis extract (PYE) on mRNA and protein levels of the pro-inflammatory chemokines, thymus, and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), in human HaCaT keratinocyte cells treated to interferon (IFN)-γ or tumor necrosis factor (TNF)-α (10 ng/mL each). The effect of the PYE on extracellular signal-regulated kinase (ERK) and other mitogen-activated protein kinases (MAPKs) was related to its suppression of TARC and MDC production by blocking NF-κB activation in HaCaT cells. Furthermore, astaxanthin and xanthophyll from P. yezoensis were identified as anti-AD candidate compounds. These results suggest that the PYE may improve AD and contained two carotenoids by regulating pro-inflammatory chemokines.
Effects of Small-Sided Recreational Volleyball on Health Markers and Physical Fitness in Middle-Aged Men

The present study aimed to investigate whether recreational volleyball organized as small-sided games could improve fitness and health profiles of middle-aged men after 10 weeks of training. Twenty-four healthy men aged 35–55 were randomized in a small-sided recreational volleyball group (RV = 12; age: 44.7 ± 6.34 years; body mass index: 25.85 ± 1.74) and control group (CON = 12; age: 42.9 ± 8.72 years; body mass index: 25.62 ± 1.48). The RV group carried out a volleyball training program, whereas the CON group continued their daily life activities during this period. The participants in the RV group performed 2/3 training sessions of 90 min per week. Results from a repeated measure ANOVA indicated a significant group × time interaction for low-density lipoprotein (LDL) cholesterol (F = 6.776, p = 0.016, partial ƞ2 = 0.235) and for resting heart rate (F = 11.647, p = 0.002, partial ƞ2 = 0.346) in favor of the RV group. No significant changes were observed for body weight, body mass index, and diastolic blood pressure. Results for physical fitness indicated a significant interaction for Yo-Yo intermittent recovery test–level 2 (F = 11.648, p = 0.003, partial ƞ2 = 0.380), with no significant changes in both groups for handgrip strength. Recreational small-sided volleyball can be an effective training modality to stimulate a decrease in LDL cholesterol and resting HR with small improvements in cardiovascular fitness. Recreational volleyball played only two times per week shows positive cardiovascular fitness and health-related adaptations, which may contribute to the reduction of the risk of developing lifestyle diseases.
A STUDY OF OSTEOCYTE APOPTOSIS BY REGION AND QUADRANT IN MURINE CORTICAL BONE

Osteocytes undergo apoptosis to spatially and temporally initiate bone remodeling. This study investigates the distribution of apoptotic osteocytes within different quadrants and regions of cortical bone and compares the frequency of osteocyte apoptosis to regional factors associated with bone remodeling. Specifically, the quantity of apoptosis was compared to levels of the bone morphagenic protein antagonists noggin and gremlin. Samples of unloaded right tibial bone obtained from C57/Bl/6 mice underwent TUNEL staining for apoptotic osteocytes and were counterstained with methyl green to detect osteocyte viability. Cross sectional areas of bone were divided into four quadrants (cranial, caudal, medial, and lateral) and three regions (proximal, midshaft, and distal) for analysis. Densities and percentages of osteocytes were measured within each area. While the results show that there were no differences among quadrants, regional variations were found in osteocyte apoptosis. A significantly higher density of apoptotic osteocytes was found in the midshaft region which also displayed higher levels of BMP antagonists. Using regression analysis, a positive linear relationship between apoptotic osteocytes and gremlin was established while noggin showed a negative linear correlation for the percentage of apoptotic osteocytes. Further studies are needed to observe the distribution of apoptotic osteocytes within loaded bone to confirm the exact relationship between osteocyte apoptosis and bone remodeling. v ACKNOWLEDGEMENTS I would like to thank Dr. Scott Hazelwood for the opportunity to work on this project. Thank you for your patience, guidance, and generosity throughout the entire process. I want to thank my committee members, Dr. Dan Wash and Dr. Lanny Griffin. I would also like to thank Scott Mosher for spending hours in the lab working side by side on our projects. I would also like to thank all the professors that contributed to my research. Thank you Dr. Lily Laiho for the training and use of your microscope, Dr. Kristen Cardinal for all the lab assistance and microtome training, and Dr. Trevor Cardinal for help with preparing, processing, and providing the subjects. Finally, I would like to thank my parents.
Inhibition of Human Breast Cancer Cell Proliferation by Low‐Intensity Ultrasound Stimulation

Cancer is characterized by uncontrolled cell proliferation, which makes novel therapies highly desired. In this study, the effects of near‐field low‐intensity pulsed ultrasound (LIPUS) stimulation on T47D human breast cancer cell and healthy immortalized MCF‐12A breast epithelial cell proliferation were investigated in monolayer cultures.
Mobile Apps for Mental Health Issues: Meta-Review of Meta-Analyses

Background Mental health apps have great potential to help people needing support to cope with distress or specific symptoms. In fact, there is an exponential increase in the number of mental health apps available on the internet, with less than 5% being actually studied. Objective This study aimed to assess the quality of the available evidence regarding the use of mental health apps and to summarize the results obtained so far. Methods Systematic reviews and meta-analyses were searched, specifically for mobile apps on mental health issues or symptoms, and rated using the Grading of Recommendations Assessment, Development and Evaluation system. Results A total of 7 meta-analyses were carefully reviewed and rated. Although some meta-analyses looked at any mental health issue and analyzed the data together, these studies were of poorer quality and did not offer strong empirical support for the apps. Studies focusing specifically on anxiety symptoms or depressive symptoms were of moderate to high quality and generally had small to medium effect sizes. Similarly, the effects of apps on stress and quality of life tended to offer small to medium effects and were of moderate to high quality. Studies looking at stand-alone apps had smaller effect sizes but better empirical quality than studies looking at apps with guidance. The studies that included follow-ups mostly found a sustained impact of the app at an 11-week follow-up. Conclusions This meta-review revealed that apps for anxiety and depression hold great promise with clear clinical advantages, either as stand-alone self-management or as adjunctive treatments. More meta-analyses and more quality studies are needed to recommend apps for other mental health issues or for specific populations.