Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacological Preconditioning Using Diazoxide Regulates Store-Operated Ca2 + Channels in Adult Rat Cardiomyocytes

Voltage-dependent Ca2+ channels and store-operated Ca2+ channels (SOCs) are the major routes of Ca2+ entry into mammalian cells. Previously, we reported that pharmacological preconditioning (PPC) leads to a decrease in the amplitude of L-type calcium channel current in the heart. In this study, we examined PPC-associated changes in SOC function. We measured adult cardiomyocyte membrane currents using the whole-cell patch-clamp technique, and we evaluated reactive oxygen species (ROS) production and intracellular Ca2+ levels in cardiomyocytes using fluorescent probes. Diazoxide (Dzx) and thapsigargin (Tg) were used to induce PPC and to deplete internal stores of Ca2+, respectively. Ca2+ store depletion generated inward currents with strong rectification, which were suppressed by the SOC blocker GSK-7975-A. These currents were completely abolished by PPC, an effect that could be countered with 5-hydroxydecanoate (5-HD; a selective mitochondrial ATP-sensitive K+ channel blocker), an intracellular mitochondrial energizing solution, or Ni2+ [a blocker of sodium–calcium exchanger (NCX)]. Buffering of ROS and intracellular Ca2+ also prevented PPC effects on SOC currents. Refilling of intracellular stores was largely suppressed by PPC, as determined by measuring intracellular Ca2+ with a fluorescent Ca2+ indicator. These results indicate that influx of Ca2+ through SOCs is inhibited by their ROS and Ca2+-dependent inactivation during PPC and that NCX is a likely source of PPC-inactivating Ca2+. We further showed that NCX associates with Orai1. Down-regulation of SOCs by PPC may play a role in cardioprotection following ischemia–reperfusion.
Can Simulated Nature Support Mental Health? Comparing Short, Single-Doses of 360-Degree Nature Videos in Virtual Reality With the Outdoors

Nature exposure in virtual reality (VR) can provide emotional well-being benefits for people who cannot access the outdoors. Little is known about how these simulated experiences compare with real outdoor experiences. We conduct an experiment with healthy undergraduate students that tests the effects of 6 min of outdoor nature exposure with 6 min of exposure to a 360-degree VR nature video, which is recorded at the outdoor nature exposure location. Skin conductivity, restorativeness, and mood before and after exposure are measured. We find that both types of nature exposure increase physiological arousal, benefit positive mood levels, and are restorative compared to an indoor setting without nature; however, for outdoor exposure, positive mood levels increase and for virtual nature, they stay the same. The nature-based experience shows benefits above and beyond the variance explained by participants’ preferences, nature and VR experiences, and demographic characteristics. Settings where people have limited access to nature might consider using VR nature experiences to promote mental health.
Cardiovascular Risks and Benefits of Medications Used for Weight Loss

Obesity is a complex disease influenced by many neurohormonal pathways which regulate body weight toward homeostasis. Presently, the disease of obesity effects over a billion individuals worldwide with scalable treatment options in dire need. Pharmacologic interventions for obesity have been developed to help promote weight loss in individuals with obesity. This area is rapidly developing and will only exponentially increase to serve the demand for persons with obesity seeking biologically orientated solutions to treat their disease. Therefore, understanding the cardiovascular risks and benefits of these weight loss medications is of particularly importance due to obesities strong association with cardiovascular (CV) disease risk. Moreover, past experiences with pharmacotherapy agents with weight loss properties have demonstrated an association with adverse CV outcomes, leading to market removal, in most cases and concerns over using similar medications. To better understand the CV risks and benefits pharmacotherapy agents used for weight loss, this review will discuss medications which are FDA-approved for weight loss, as well as medications commonly used off-label for this indication. The goal is to provide an overview of the risks and benefits many of these medications can offer to help guide clinical decision making and patient education.
Graphene Oxide Mediated Broad-Spectrum Antibacterial Based on Bimodal Action of Photodynamic and Photothermal Effects

Graphene oxide (GO) with their interesting properties including thermal and electrical conductivity and antibacterial characteristics have many promising applications in medicine. The prevalence of resistant bacteria is considered a public health problem worldwide, herein, GO has been used as a broad spectrum selective antibacterial agent based on the photothermal therapy (PTT)/photodynamic therapy (PDT) effect. The preparation, characterization, determination of photophysical properties of two different sizes of GO is described. In vitro light dose and concentration-dependent studies were performed using Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria based on the PTT/PDT effect used ultra-low doses (65 mW cm–2) of 630 nm light, to achieve efficient bacterial decontamination. The results show that GO and nanographene oxide (nGO) can sensitize the formation of 1O2 and allow a temperature rise of 55°C to 60°C together nGO and GO to exert combined PTT/PDT effect in the disinfection of gram-positive S. aureus and gram-negative E. coli bacteria. A complete elimination of S. aureus and E. coli bacteria based on GO and nGO is obtained by using a dose of 43–47 J cm–2 for high concentration used in this study, and a dose of around 70 J cm–2 for low dose of GO and nGO. The presence of high concentrations of GO allows the bacterial population of S. aureus and E. coli to be more sensitive to the use of PDT/PTT and the efficiency of S. aureus and E. coli bacteria disinfection in the presence of GO is similar to that of nGO. In human neonatal dermal fibroblast, HDFs, no significant alteration to cell viability was promoted by GO, but in nGO is observed a mild damage in the HDFs cells independent of nGO concentration and light exposure. The unique properties of GO and nGO may be useful for the clinical treatment of disinfection of broad-spectrum antimicrobials. The antibacterial results of PTT and PDT using GO in gram-positive and gram-negative bacteria, using low dose light, allow us to conclude that GO and nGO can be used in dermatologic infections, since the effect on human dermal fibroblasts of this treatment is low compared to the antibacterial effect. GRAPHICAL ABSTRACT PTT/PTT effect due to irradiation with red LED of GO and nGO in the presence of E. coli and S. aureus bacteria.
Aging Disrupts the Circadian Patterns of Protein Expression in the Murine Hippocampus

Aging is associated with cognitive decline and dysregulation of the circadian system, which modulates hippocampal-dependent memory as well as biological processes underlying hippocampal function. While circadian dysfunction and memory impairment are common features of aging and several neurodegenerative brain disorders, how aging impacts the circadian expression patterns of proteins involved in processes that underlie hippocampal-dependent memory is not well understood. In this study, we profiled the hippocampal proteomes of young and middle-aged mice across two circadian cycles using quantitative mass spectrometry in order to explore aging-associated changes in the temporal orchestration of biological pathways. Of the ∼1,420 proteins that were accurately quantified, 15% (214 proteins) displayed circadian rhythms in abundance in the hippocampus of young mice, while only 1.6% (23 proteins) were rhythmic in middle-aged mice. Remarkably, aging disrupted the circadian regulation of proteins involved in cellular functions critical for hippocampal function and memory, including dozens of proteins participating in pathways of energy metabolism, neurotransmission, and synaptic plasticity. These included processes such as glycolysis, the tricarboxylic acid cycle, synaptic vesicle cycling, long-term potentiation, and cytoskeletal organization. Moreover, aging altered the daily expression rhythms of proteins implicated in hallmarks of aging and the pathogenesis of several age-related neurodegenerative brain disorders affecting the hippocampus. Notably, we identified age-related alterations in the rhythmicity of proteins involved in mitochondrial dysfunction and loss of proteostasis, as well as proteins involved in the pathogenesis of disorders such as Alzheimer’s disease and Parkinson’s disease. These insights into aging-induced changes in the hippocampal proteome provide a framework for understanding how the age-dependent circadian decline may contribute to cognitive impairment and the development of neurodegenerative diseases during aging.
Influence of Neighboring Clonal-Colonies on Aflatoxin Production by Aspergillus flavus

Aspergillus flavus is an ascomycete fungus that infects and contaminates corn, peanuts, cottonseed, and treenuts with acutely toxic and carcinogenic aflatoxins. The ecological function of aflatoxin production is not well understood; though not phytotoxic, aflatoxin may be involved in resisting oxidative stress responses from infection or drought stress in plants. Observation of aflatoxin stimulation in 48-well plates in response to increasing inoculated wells sparked an investigation to determine if A. flavus volatiles influence aflatoxin production in neighboring colonies. Experiments controlling several culture conditions demonstrated a stimulation of aflatoxin production with increased well occupancy independent of pH buffer, moisture, or isolate. However, even with all wells inoculated, aflatoxin production was less in interior wells. Only one isolate stimulated aflatoxin production in a large Petri-dish format containing eight small Petri dishes with shared headspace. Other isolates consistently inhibited aflatoxin production when all eight Petri dishes were inoculated with A. flavus. No contact between cultures and only shared headspace implied the fungus produced inhibitory and stimulatory gases. Adding activated charcoal between wells and dishes prevented inhibition but not stimulation indicating stimulatory and inhibitory gases are different and/or gas is inhibitory at high concentration and stimulatory at lower concentrations. Characterizing stimulatory and inhibitory effects of gases in A. flavus headspace as well as the apparently opposing results in the two systems deserves further investigation. Determining how gases contribute to quorum sensing and communication could facilitate managing or using the gases in modified atmospheres during grain storage to minimize aflatoxin contamination.
Editorial: Balancing Act: Structural-Functional Circuit Disruptions and Compensations in Developing and Aging Brain Disorders

1 The Key Laboratory of Biomedical Information Engineering, Ministry of Education, Department of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, China, 2 School of Automation, Northwestern Polytechnical University, Xi’an, China, 3 Key Laboratory of Brain and Education, Nanning Normal University, Nanning, China, Department of Psychology, University of Chinese Academy of Sciences, Beijing, China, 5 J. Crayton Pruitt Family
A Novel Calcium-Activated Potassium Channel Controls Membrane Potential and Intracellular pH in Trypanosoma cruzi

Trypanosoma cruzi develops in environments where nutrient availability, osmolarity, ionic concentrations, and pH undergo significant changes. The ability to adapt and respond to such conditions determines the survival and successful transmission of T. cruzi. Ion channels play fundamental roles in controlling physiological parameters that ensure cell homeostasis by rapidly triggering compensatory mechanisms. Combining molecular, cellular and electrophysiological approaches we have identified and characterized the expression and function of a novel calcium-activated potassium channel (TcCAKC). This channel resides in the plasma membrane of all 3 life stages of T. cruzi and shares structural features with other potassium channels. We expressed TcCAKC in Xenopus laevis oocytes and established its biophysical properties by two-electrode voltage clamp. Oocytes expressing TcCAKC showed a significant increase in inward currents after addition of calcium ionophore ionomycin or thapsigargin. These responses were abolished by EGTA suggesting that TcCAKC activation is dependent of extracellular calcium. This activation causes an increase in current and a negative shift in reversal potential that is blocked by barium. As predicted, a single point mutation in the selectivity filter (Y313A) completely abolished the activity of the channels, confirming its potassium selective nature. We have generated knockout parasites deleting one or both alleles of TcCAKC. These parasite strains showed impaired growth, decreased production of trypomastigotes and slower intracellular replication, pointing to an important role of TcCAKC in regulating infectivity. To understand the cellular mechanisms underlying these phenotypic defects, we used fluorescent probes to evaluate intracellular membrane potential, pH, and intracellular calcium. Epimastigotes lacking the channel had significantly lower cytosolic calcium, hyperpolarization, changes in intracellular pH, and increased rate of proton extrusion. These results are in agreement with previous reports indicating that, in trypanosomatids, membrane potential and intracellular pH maintenance are linked. Our work shows TcCAKC is a novel potassium channel that contributes to homeostatic regulation of important physiological processes in T. cruzi and provides new avenues to explore the potential of ion channels as targets for drug development against protozoan parasites.
Surface Antigen 1 Is a Crucial Secreted Protein That Mediates Babesia microti Invasion Into Host Cells

Babesia microti, a tick-borne intraerythrocytic zoonotic protozoan, causes most of human babesiosis in the world, and patients usually experience intermittent fever, fatigue, and chills, followed by a combination of additional symptoms and even death in severe cases. Unfortunately, there is no curable drug or effective vaccine available, and the mechanism of related virulence factors in invasion to host cells during the merozoite stage is unclear. Here, we evaluated a secreted protein annotated as B. microti surface antigen 1 (BmSA1) and identified from in vitro culture supernatant by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). BmSA1 fragment was expressed in Escherichia coli to prepare polyclonal antiserum. Western blot analysis revealed the existence of BmSA1 in the lysate of the parasites and the hemolysate of infected red blood cells (iRBCs). Laser confocal microscopy confirmed BmSA1 as a secreted protein with diffuse distribution around the parasites in red blood cells (RBCs). The adhesion capacity of BmSA1 against the host RBCs was tested by RBC binding assays using the recombinant BmSA1 protein (rBmSA1), which was shown to specifically bind to host RBCs. Further in vitro antiserum-neutralization test demonstrated that the growth of parasites could be significantly inhibited by the anti-BmSA1 antiserum. These results indicate that BmSA1 is a crucial factor for B. microti invasion into host RBCs with an important role in host-parasite interactions during the merozoite stage and has the potential use as a vaccine candidate due to its high secretion amount.
TriPCE: A Novel Tri-Clustering Algorithm for Identifying Pan-Cancer Epigenetic Patterns

Epigenetic alteration is a fundamental characteristic of nearly all human cancers. Tumor cells not only harbor genetic alterations, but also are regulated by diverse epigenetic modifications. Identification of epigenetic similarities across different cancer types is beneficial for the discovery of treatments that can be extended to different cancers. Nowadays, abundant epigenetic modification profiles have provided a great opportunity to achieve this goal. Here, we proposed a new approach TriPCE, introducing tri-clustering strategy to integrative pan-cancer epigenomic analysis. The method is able to identify coherent patterns of various epigenetic modifications across different cancer types. To validate its capability, we applied the proposed TriPCE to analyze six important epigenetic marks among seven cancer types, and identified significant cross-cancer epigenetic similarities. These results suggest that specific epigenetic patterns indeed exist among these investigated cancers. Furthermore, the gene functional analysis performed on the associated gene sets demonstrates strong relevance with cancer development and reveals consistent risk tendency among these investigated cancer types.
Sympathetic Activation in Hypertensive Chronic Kidney Disease – A Stimulus for Cardiac Arrhythmias and Sudden Cardiac Death?

Studies have revealed a robust and independent correlation between chronic kidney disease (CKD) and cardiovascular (CV) events, including death, heart failure, and myocardial infarction. Recent clinical trials extend this range of adverse CV events, including malignant ventricular arrhythmias and sudden cardiac death (SCD). Moreover, other studies point out that cardiac structural and electrophysiological changes are a common occurrence in this population. These processes are likely contributors to the heightened hazard of arrhythmias in CKD population and may be useful indicators to detect patients who are at a higher SCD risk. Sympathetic overactivity is associated with increased CV risk, specifically in the population with CKD, and it is a central feature of the hypertensive state, occurring early in its clinical course. Sympathetic hyperactivity is already evident at the earliest clinical stage of CKD and is directly related to the progression of renal failure, being most pronounced in those with end-stage renal disease. Sympathetic efferent and afferent neural activity in kidney failure is a crucial facilitator for the perpetuation and evolvement of the disease. Here, we will revisit the role of the feedback loop of the sympathetic neural cycle in the context of CKD and how it may aggravate several of the risk factors responsible for causing SCD. Targeting the overactive sympathetic nervous system therapeutically, either pharmacologically or with newly available device-based approaches, may prove to be a pivotal intervention to curb the substantial burden of cardiac arrhythmias and SCD in the high-risk population of patients with CKD.
Effects of Different Training Intensity Distribution in Recreational Runners

Purpose: To compare the impact of two different training intensity distributions in terms of conditional and performance parameters and spent time to training in recreational athletes. Methods: Two different training intensity distribution model were performed for 8 weeks by 38 recreational runners. Runners recruited were randomly assigned to 2 different training models based on HR intensity detected with maximal test. The percentage distribution splitted in zone 1, 2, and 3 were by 77/3/20 and 40/50/10 in polarized endurance training group (PET) and focused endurance training (FOC) group, respectively. Programs were balanced for total training impulse (TRIMP). To evaluate effects of training, before and after treatment were performed a maximal exercise test to determine Maximal Oxygen Uptake (V'O2max), Ventilatory Threshold (VT), respiratory-compensation point (RCT) Running Economy (RE), and 2 Km performance. To investigate the effects of training on muscular performance were performed one repetition maximum (1 RM), squat jump (SJ), and counter movement jump (CMJ). Results: Both groups significantly improved their velocity at V'O2max (3.2 and 4.0%), at VT (4.0 and 3.2%), RCT (5.7 and 3.4%), the average velocity in 2 Km performance (3.5 and 3.0%) and RE (−5.3 and −8.7%) for PET and FOC, respectively for each variable. No differences were found between the groups on any parameter investigated except about the total training time (PET = 29.9 ± 3.1 h and FOC = 24.8 ± 2.0 h). Conclusion: Focused Endurance Training obtains similar improvements than Polarized Endurance Training saving 17% of training time in recreational runners.
Theoretical Study on the Sensing Mechanism of Novel Hydrazine Sensor TAPHP and Its ESIPT and ICT Processes

The photophysical and photochemical properties of the novel hydrazine sensor TAPHP and the TAPDP generated by the cyclization reaction of TAPHP with hydrazine are investigated using the density functional theory and time-dependent density functional theory. The results show that both the excited-state intramolecular proton transfer and intramolecular charge transfer can occur for TAPHP and TAPDP. Analysis of bond parameters and infrared vibrational spectra indicate that hydrogen bonds are enhanced in the first excited state, which is beneficial to excited-state intramolecular proton transfer. The strength of hydrogen bonds is also visualized by using the independent gradient model and topological analysis. The core-valence bifurcation index and bond critical point parameters are further employed to measure hydrogen bonds. The reaction path of proton transfer is obtained through the potential energy curves. The excitation of TAPHP and TAPDP is attributed to the charge transfer excitation, which is determined by the characteristics of the hole-electron distribution. The reaction site and product configuration are verified by atomic charge and 1H-NMR spectra. The negative free energy difference indicates that the reaction between TAPHP and hydrazine can proceed spontaneously. In addition, the absorption and fluorescence spectra agree well with the experimental results, confirming that TAPHP is an excellent sensor of hydrazine.
Enhanced Cell Division Is Required for the Generation of Memory CD4 T Cells to Migrate Into Their Proper Location

CD4 T cell memory is fundamental for long-lasting immunity and effective secondary responses following infection or vaccination. We have previously found that memory CD4 T cells specific for systemic antigens preferentially reside in the bone marrow (BM) and arise from splenic CD49b+T-bet+ CD4 T cells. However, how BM-homing memory precursors are generated during an immune reaction is unknown. We show here that BM memory precursors are generated via augmented rates of cell division throughout a primary immune response. Treatment with the cytostatic drug cyclophosphamide or blockade of the CD28/B7 co-stimulatory pathway at the beginning of the contraction phase abrogates the generation of BM memory precursors. We determine that, following a critical number of cell divisions, memory precursors downregulate CCR7 and upregulate IL-2Rβ, indicating that loss of CCR7 and gain of IL-2 signal are required for the migration of memory precursors toward the BM.