Phase Of Cycle Research Articles

Analysis of Liquefaction in Tailings Deposits by Fem Modeling of Undrained Cyclic Triaxial

In this article, a numerical calibration procedure for undrained cyclic triaxial tests is presented to evaluate the liquefaction potential in sand and silt samples from mining tailings in northern Chile. The numerical modeling of an axisymmetric specimen involved two stages: isotropic consolidation using the Hardening Soil Small (HSS) model and a cycling phase employing the UBC3D-PLM model to simulate the onset of liquefaction using the criterion that the excess pore pressure ratio Ru should exceed 0.8. The results demonstrate that the UBC3D-PLM modeling calibrated with experimental data from cyclic triaxial tests effectively represents the excess pore pressure in both sandy and silty soils from mining tailings. The accuracy of the modeling decreases when a single set of parameters is applied to the same soil at different cyclic stress ratios (CSR), highlighting the need for specific calibrations for each loading.

Inorganic Polyphosphate Promotes Colorectal Cancer Growth via TRPM8 Receptor Signaling Pathway

Background: Colorectal cancer (CRC) is characterized by a pro-inflammatory microenvironment and features high-energy-supply molecules that assure tumor growth. A still less studied macromolecule is inorganic polyphosphate (iPolyP), a high-energy linear polymer that is ubiquitous in all forms of life. Made up of hundreds of repeated orthophosphate units, iPolyP is essential for a wide variety of functions in mammalian cells, including the regulation of proliferative signaling pathways. Some evidence has suggested its involvement in carcinogenesis, although more studies need to be pursued. Moreover, iPolyP regulates several homeostatic processes in animals, spanning from energy metabolism to blood coagulation and tissue regeneration. Results: In this study, we tested the role of iPolyP on CRC proliferation, using in vitro and ex vivo approaches, in order to evaluate its effect on tumor growth. We found that iPolyP is significantly increased in tumor tissues, derived from affected individuals enrolled in this study, compared to the corresponding peritumoral counterparts. In addition, iPolyP signaling occurs through the TRPM8 receptor, a well-characterized Na+ and Ca2+ ion channel often overexpressed in CRC and linked with poor prognosis, thus promoting CRC cell proliferation. The pharmacological inhibition of TRPM8 or RNA interference experiments performed in established CRC cell lines, such as Caco-2 and SW620, showed that the involvement of TRPM8 is essential, greater than that of the other two known iPolyP receptors, P2Y1 and RAGE. The presence of iPolyP drives cancer cells towards the mitotic phase of the cell cycle by enhancing the expression of ccnb1, which encodes the Cyclin B protein. In vitro 2D and 3D data reflected the ex vivo results, obtained by the generation of CRC-derived organoids, which increased in size. Conclusions: These results indicate that iPolyP may be considered a novel and unexpected early biomarker supporting colorectal cancer cell proliferation.

Dynamics of the Pre-Powerstroke Myosin Lever Arm and the Effects of Omecamtiv Mecarbil.

The binding of small molecules to sarcomeric myosin can elicit powerful effects on the chemomechanical cycle, making them effective therapeutics in the clinic and research tools at the benchtop. However, these myotropes can have complex effects that act on different phases of the crossbridge cycle and which depend on structural, dynamic, and environmental variables. While small molecule binding sites have been identified crystallographically and their effects on contraction studied extensively, small molecule-induced dynamic changes that link structure-function are less studied. Here, we use molecular dynamics simulations to explore how omecamtiv mecarbil (OM), a cardiac myosin-specific myotrope, alters the coordinated dynamics of the lever arm and the motor domain in the pre-powerstroke state. We show that the lever arm adopts a range of orientations and find that different lever arm orientations are accompanied by changes in the hydrogen bonding patterns near the converter. We find that the binding of OM to myosin reduces the conformational heterogeneity of the lever arm orientation and also adjusts the average lever arm orientation. Finally, we map out the distinct conformations and ligand-protein interactions adopted by OM. These results uncover some structural factors that govern the motor domain-tail orientations and the mechanisms by which OM primes the pre-powerstroke myosin heads.

Influence of quasi-biennial oscillations (QBO) on the stratospheric polar vortex in the Antarctic

For many years, the dominant opinion in the literature has been that the stratospheric polar vortex is weaker in the easterly phase of the QBO than in the westerly phase, which is known as the Holton–Tan effect. While for the Northern Hemisphere vortex this is true during winter, for the Southern Hemisphere vortex the dependence on the QBO is observed only in spring. This feature is usually explained by the greater intensity of the Southern Hemisphere vortex compared to the Northern Hemisphere vortex, and the QBO can modulate its strength only during the vortex breaking season in October-November. Usually, the vortex response to the QBO is determined based on the equatorial wind direction at a certain vertical level, and the conclusions depend strongly on the level at which the QBO phase is determined. However, it has long been shown that using the equatorial wind sign at one or even a combination of several levels is not quite correct because it does not take into account the time of descent of the QBO wind relative to the seasons of the year, and it is not known at what altitudes the QBO wind has the strongest influence on the extratropical stratosphere. Due to the variable period of the QBO cycles, the phase relationship between the seasonal cycle and the QBO cycle is constantly changing, resulting in many variants of the vertical structure of the wind QBO during the Antarctic winter vortex and ozone hole. However, the seasonal regularities of QBO used in this work lead to a strictly limited number of possible variants of coincidence of the phases of the QBO cycles with the seasons of the year, which allows us to reveal typical features of interannual variations of the polar vortex and ozone hole in the Antarctic that are due to the QBO. The analysis of observational data indicates unexpected peculiarities of the QBO modulation of the stratospheric polar vortex in the Antarctic. The QBO effect in the vortex intensity is observed not only in spring during the weakening phase of the winter vortex, but also during the vortex maximum in June–August. At the same time, changes in the wind speed of the vortex during its maximum in winter are opposite to those in the spring during the ozone hole period. If the winter vortex is more intense (weak), then during the ozone hole period the vortex is weaker (more intense) than the average level.

The cytotoxic activities of the major diterpene extracted from Salvia multicaulis (Bardakosh) are mediated by the regulation of heat-shock response and fatty acid metabolism pathways in human leukemia cells

BackgroundLeukemia is one of the most lethal cancers worldwide and represents the sixth-leading cause of cancer deaths. The results of leukemia treatment have not been as positive as desired, and recurrence is common. PurposeThus, there is an urgent requirement for the development of new therapeutic drugs. Salvia multicaulis (Bardakosh) is a widespread species that contains multiple phytochemical components with anti-cancer activities. MethodsWe isolated and characterized the major diterpene candesalvone B methyl ester from S. multicaulis and investigated its action as a cytotoxic agent towards sensitive and drug-resistant leukemia cells by the resazurin reduction assay. Additionally, the targeted genes and the affected molecular mechanisms attributed to the potent cytotoxic activities were discovered by transcriptome-wide mRNA expression profiling. The targets predicted to be regulated by candesalvone B methyl ester in each cell line were confirmed by qRT-PCR, molecular docking, microscale thermophoresis, and western blotting. Moreover, cell cycle distribution and apoptosis were analyzed by flow cytometry. ResultsCandesalvone B methyl ester was cytotoxic with IC50 values of 20.95 ± 0.15 µM against CCRF-CEM cells and 4.13 ± 0.10 µM against multidrug-resistant CEM/ADR5000 leukemia cells. The pathway enrichment analysis disclosed that candesalvone B methyl ester could regulate the heat-shock response signaling pathway via targeting heat shock factor 1 (HSF1) in CCRF-CEM cells and ELOVL fatty acid elongase 5 (ELOVL5) controls the fatty acid metabolism pathway in CEM/ADR5000 cells. Microscale thermophoresis showed the binding of candesalvone B methyl ester with HSF1 and ELOVL5, confirming the results of molecular docking analysis. Down-regulation of both HSF1 and ELOVL5 by candesalvone B methyl ester as detected by both western blotting and RT-qPCR was related to the reversal of drug resistance in the leukemia cells. Furthermore, candesalvone B methyl ester increased the arrest in the sub-G1 phase of the cell cycle in a dose-dependent manner from 1.3 % to 32.3 % with concomitant induction of apoptosis up to 29.0 % in CCRF-CEM leukemic cells upon inhibition of HSF1. ConclusionCandesalvone B methyl ester isolated from S. multicaulis exerted cytotoxicity by affecting apoptosis, cell division, and modulation of expression levels of genes contributing to the heat stress signaling and fatty acid metabolism pathways that could relieve drug resistance of leukemia cells.

Expression of the apelin system in the porcine pituitary during the oestrous cycle and early pregnancy and the effect of apelin on LH and FSH secretion

Reproductive success requires considerable energy investment. Research has shown that some adipokines, i.e. the hormones produced in adipose tissue, affect reproductive functions by influencing all structures of the hypothalamic-pituitary-ovarian axis. Apelin is a recently identified member of the adipokine family. To the best of the authors' knowledge, this is the first study to investigate the gene and protein expression of the apelin system (the apelin hormone and the apelin receptor, APJ) in the anterior (AP) and posterior (PP) pituitary lobes of the domestic pig during different phases of the oestrous cycle (days 2 to 3, 10 to 12, 14 to 16, and 17 to 19) and in early pregnancy (days 10 to 11, 12 to 13, 15 to 16, and 27 to 28). It was also assumed that apelin participates in the regulation of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion and influences Akt, MAPK/Erk1/2, and AMPK signalling pathways in the AP during the oestrous cycle. Apelin, APJ mRNAs and proteins were detected in both pituitary lobes. Apelin was identified in gonadotropes, somatotropes, lactotropes, and thyrotropes. The study also revealed that apelin and APJ mRNA/protein levels fluctuate during the oestrous cycle and early gestation. Apelin affects basal, GnRH- and/or insulin-stimulated gonadotropin secretion in some phases of the cycle, as well as the phosphorylation of Akt, MAPK/Erk1/2, and AMPK proteins in AP cells. These findings suggest that apelin may be produced locally in the pituitary and that this gland is receptive to apelin's action. The study also suggest that apelin may influence female reproductive functions by controlling the release of LH and FSH from AP cells, and that it affects Akt, MAPK/Erk1/2, and AMPK signalling pathways.

Bladder Responses to Thoracolumbar Epidural Stimulation in Female Urethane-Anesthetized Rats with Graded Contusion Spinal Cord Injuries.

Spinal cord epidural stimulation (scES) is a therapeutic option that promotes functional improvements in sensory, motor, and autonomic functions following spinal cord injury (SCI). Previous scES mapping studies targeting the lower urinary tract (LUT) in rats demonstrated functional response variability based upon lumbosacral level, parameters used, extent of injury (spinally intact vs. chronic anatomically complete spinal transections), and sex. In the current study, female rats with clinically relevant graded incomplete T9 contusion injuries were mapped with scES at 60 days post-injury at three spinal levels (T13, L3, L6) with a novel miniature 15-electrode array designed to deliver optimal specificity. The results obtained during bladder fill and void cycles conducted under urethane anesthesia indicate frequency dependent sub-motor threshold effects on LUT function with a single row of electrodes positioned across the full medio-lateral extent of the dorsal cord. The findings of improved storage and emptying, represented by significantly longer inter-contractile intervals with T13 scES and L3 scES and by a significantly increased estimated void efficiency with L6 scES, respectively, are consistent with previous studies using intact and chronic complete transected male and female rats. The data support the efficacy of selective spinal network stimulation to drive functionally relevant networks for storage versus emptying phases of the urinary cycle. The current findings further demonstrate the translational promise of scES for SCI individuals with LUT dysfunctions, regardless of injury severity.

Interactive effects of dietary energy levels with amino acid density on growth performance and optimal digestible Lys to energy ratio of male broiler chickens

A total of 2,400 day-old off-sex male Ross 308 chicks were used in a 4 × 3 factorial array (8 replicates with 25 birds per replicate) to determine the interactive effects of dietary metabolizable energy (ME) and amino acid (AA) densities on productive traits of broiler chickens reared to 42 d of age. The experimental factors were 4 ME levels (control, -50, -100, -150 kcal) and 3 digestible AA levels (control, +3.0 and +6.0%). Diets were fed for starter (0-10 d), grower (11-24 d), finisher (25-35 d), and withdrawal (36-42 d) phases, with consistent reduction of ME and increase in AA density for each phase. Overall, ME reduction did not compromise final body weight (BW; d 42). However, when ME was reduced by 50 kcal, only the diets with +6% AA density improved BW, resulting in an interaction between ME and AA levels (P < 0.05). Reducing ME and increasing AA densities independently increased total feed intake (P < 0.01). An interaction between ME and AA density on feed conversion ratio (FCR) was observed where increasing AA density at both +3.0 and +6.0% levels at control ME reduced FCR, but with reduced ME diets, FCR was reduced only at +6% AA density (P < 0.01). Quadratic broken line models estimated a digestible Lys to ME ratio (mg Lys/1,000 kcal ME) of 474 and 407 in starter and grower diets, respectively, to optimize both BW and FCR. However, in finisher phase a ratio of 363 could only be predicted for optimal FCR and in withdrawal a ratio of 349 to optimize BW. In summary, these results indicate that the interaction between ME and AA densities affects the productive traits of broiler chickens. Increasing AA density at control ME density improves FCR, while reduced ME diets require higher AA density to improve FCR. Quadratic broken line models suggest specific digestible Lys to ME ratios for optimizing BW and FCR across different phases of the production cycle.

Unveiling the carbon footprint of True Neapolitan Pizza: paving the way for eco-friendly practices in pizzerias

This study investigated the environmental ramifications in the production and consumption of pizza. The PAS 2050 standard methodology was used to quantify the cradle-to-grave carbon footprint of a typical medium-sized Neapolitan pizzeria offering both table service and takeaway in cardboard boxes. A spectrum of sustainable practices capable of mitigating the greenhouse gas (GHG) emissions of pizzerias was analyzed. By accounting for consistent GHG emissions across specific life cycle phases—such as energy consumption, refrigerant gas leakage, detergent production, and wastewater treatment—it was possible to estimate the cradle-to-grave carbon footprint of different iterations of the True Neapolitan Pizza. For instance, the Marinara pizza had a carbon footprint of approximately 1.7 kg CO2e/kg while the Margherita pizza topped with mozzarella cheese registered roughly twice that figure. Moreover, garnishing the Margherita with buffalo mozzarella increased its carbon footprint to 4.2 kg CO2e/kg. This difference in environmental impact can be chiefly attributed to the condiments of vegetable or animal origin, with variations in protein and fat content significantly influencing the energy value of each pizza variant. These findings emphasized the importance of informed decisions for a greener culinary future, highlighting the critical role of ingredient choices in shaping the sustainability profile of pizza offerings.

Differential expression of HIV target cells CCR5 and α4β7 in tissue resident memory CD4 T cells in endocervix during the menstrual cycle of HIV seronegative women.

Ovarian hormones are known to modulate the immune system in the female genital tract (FGT). We sought to define the impact of the menstrual cycle on the mucosal HIV target cell levels, and tissue-resident CD4 T cells. Here, we characterized the distribution, phenotype, and function of CD4 T cells with special emphasis on HIV target cells (CCR5+ and α4β7+) as well as tissue-resident memory (TRM; CD69+ and CD103+) CD4 T cells in FGT of cycling women. Peripheral blood and Endocervical cells (EC-collected from cytobrush) were collected from 105 healthy women and performed multicolor flow cytometry to characterize the various subsets of CD4 T cells. Cervicovaginal lavage (CVL) were collected for cytokine analysis and plasma were collected for hormonal analysis. All parameters were compared between follicular and luteal phase of menstrual cycle. Our findings revealed no significant difference in the blood CD4 T cell subsets between the follicular and luteal phase. However, in EC, the proportion of several cell types was higher in the follicular phase compared to the luteal phase of menstrual cycle, including CCR5+α4β7-cells (p=0.01), CD69+CD103+ TRM (p=0.02), CCR5+CD69+CD103+ TRM (p=0.001) and FoxP3+ CD4 T cells (p=0.0005). In contrast, α4β7+ CCR5- cells were higher in the luteal phase (p=0.0004) compared to the follicular phase. In addition, we also found that hormonal levels (P4/E2 ratio) and cytokines (IL-5 and IL-6) were correlated with CCR5+ CD4 T cells subsets during the follicular phase of the menstrual cycle. Overall, these findings suggest the difference in the expression of CCR5 and α4β7 in TRM CD4 T cell subsets in endocervix of HIV seronegative women between the follicular and luteal phase. Increase in the CCR5+ expression on TRM subsets could increase susceptibility to HIV infection during follicular phase of the menstrual cycle.

Dissecting dormancy and quiescence in hematopoietic stem cells

Quiescence is a fundamental state of adult hematopoietic stem cells (HSCs) characterized by their residence in the G0 phase of the cell cycle. Despite being quiescent, HSCs retain their capacities for self-renewal and multipotency, enabling them to produce all blood lineages. Recent discoveries have shown that HSCs can dive into an even deeper state of quiescence with a very low division rate in steady-state conditions, known as dormancy. Dormant HSCs (dHSCs) have the most superior stem cell properties among HSCs, placing them at the top of the hematopoietic hierarchy. In this review, we argue that quiescence and dormancy are not synonyms in the context of HSCs. Specifically, dHSCs constitute a unique reserve pool of HSCs, mobilized only under stress conditions to protect the HSC compartment throughout life. While HSC quiescence is well-studied, the molecular features of HSC dormancy remain less well-defined. We will discuss the available methods for dHSC isolation and summarize the latest findings on the roles of niche factors, transcription factors, chromatin regulators, and cell cycle-related proteins in maintaining HSC dormancy. Additionally, we will explore whether insights from the quiescent HSC research can be applied to dHSCs. Lastly, we will assess the therapeutic potential of utilizing or targeting dHSCs to improve stem cell transplantation outcomes and treat hematological diseases, opening new avenues for research and clinical applications in regenerative medicine and oncology.

Influence of Menstrual Phase and Symptoms on Match Running in Professional Footballers.

This study examined the effects of menstrual cycle phases and symptoms on match running performance in football (soccer) players. Twenty-one nonhormonal contraceptive using football players from four professional teams were monitored for up to four menstrual cycles during a domestic league season. Menstrual phases, classified as early-follicular phase (EFP), mid-late follicular phase (MFP), and luteal phase (LP), were determined by self-reporting of menstruation and urinary hormone tests (luteinizing hormone and pregnanediol-3-glucuronide). On match day, players completed a menstrual symptom severity questionnaire. In repeated matches, players wore 10 Hz Global Positioning Satellite (GPS) devices to measure relative (/min) total distance, high-speed running distance, very high-speed distance, peak speed, acceleration count, and deceleration count. Linear mixed models were performed for each GPS measure to determine the relationship with phase or symptoms. Data for 7 and 10 players were included for menstrual phase and menstrual symptoms analyses, respectively. A significantly higher total distance was reported during MFP compared to EFP (Δ 5.1 m min-1; p = 0.04) and LP (Δ 5.8 m min-1; p = 0.007). Significantly greater high-speed running was reported during MFP compared to EFP (Δ 1.2 m min-1; p = 0.012) and LP (Δ 1.1 m min-1; p = 0.007). No significant effect of menstrual phase was found for any other GPS measures (p > 0.05). Accelerations declined with increasing symptom severity (p = 0.021, estimate = -0.01count.min-1). Menstrual symptom severity did not affect any other GPS measures (p > 0.05). In conclusion, greater total distance and high-speed running occurred during the MFP. Additionally, accelerations minimally decreased with increasing menstrual symptom severity. Large intra- and inter-variability existed, suggesting individualized monitoring and management of menstrual effects on performance would be beneficial.

PLK1 Inhibitor Onvansertib Enhances the Efficacy of Alpelisib in PIK3CA-Mutated HR-Positive Breast Cancer Resistant to Palbociclib and Endocrine Therapy: Preclinical Insights.

Endocrine therapy (ET) combined with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) is the preferred first-line treatment for hormone receptor-positive (HR+)/HER2- metastatic breast cancer. Although this is beneficial, acquired resistance leads to disease progression, and patients harboring PIK3CA mutations are treated with targeted therapies such as the PI3Kα inhibitor, alpelisib, alongside ET. Drug-associated resistance mechanisms limit the efficacy of alpelisib, highlighting the need for better combination therapies. This study aimed to evaluate the efficacy of combining alpelisib with a highly specific PLK1 inhibitor, onvansertib, in PIK3CA-mutant HR+ breast cancer preclinical models. We assessed the effect of the alpelisib and onvansertib combination on cell viability, PI3K signaling pathway, cell cycle phase distribution and apoptosis in PI3K-activated HR+ breast cancer cell lines. The antitumor activity of the combination was evaluated in three PIK3CA-mutant HR+ breast cancer patient-derived xenograft (PDX) models, resistant to ET and CDK4/6 inhibitor palbociclib. Pharmacodynamics studies were performed using immunohistochemistry and Simple Western analyses in tumor tissues. The combination synergistically inhibited cell viability, suppressed PI3K signaling, induced G2/M arrest and apoptosis in PI3K-activated cell lines. In the three PDX models, the combination demonstrated superior anti-tumor activity compared to the single agents. Pharmacodynamic studies confirmed the inhibition of both PLK1 and PI3K activity and pronounced apoptosis in the combination-treated tumors. Our findings support that targeting PLK1 and PI3Kα with onvansertib and alpelisib, respectively, may be a promising strategy for patients with PIK3CA-mutant HR+ breast cancer failing ET + CDK4/6i therapies and warrant clinical evaluation.

Experimental substantiation of the methodology for the development of physical qualities women of mature age (45-55 years)

This article deals with issues aimed at the development of middle-aged women who are able to stimulate the endurance of the abdominal press, the flexibility of the hamstrings, and the muscular endurance of the upper body after 12 weeks of physical exercises for two sessions of 60 minutes per week. Squats and push-ups increase strength and muscular endurance. A woman's physical condition is also largely tied to the phases of the menstrual cycle. At the same time, the manifestation of changes in the body of women during this period is very diverse. Menstrual health is a state of complete physical, mental and social well-being, and not just the absence of diseases or ailments associated with the menstrual cycle. This is the process of preparing the body for pregnancy. Menstrual health has a huge impact on society, from the impact on careers and opportunities to health issues. Menstruation greatly affects the physical performance of athletes due to symptoms such as cramps, back pain, headache and bloating. In addition, statistics claim that 75% of women who engage in any type of physical activity experience negative side effects due to their menstrual cycle. During menstruation, women suffer from several physical, psychological, and behavioral symptoms that often result from premenstrual syndrome (PMS). Approximately 75% of women suffer from PMS and may experience headaches, abdominal cramps, bloating, fatigue, anxiety, high stress levels, or a combination of these symptoms. These symptoms range from mild to so severe that some women take days off work. While this is difficult for women to deal with in general, it affects athletes even more, who often have to go through rigorous training and physical exertion on a daily basis.

Antitumoral and Antiproliferative Potential of Synthetic Derivatives of Scorpion Peptide IsCT1 in an Oral Cavity Squamous Carcinoma Model.

The oral cavity is a frequent site for head and neck cancers, which rank as the sixth most common cancer globally, with a 5-year survival rate slightly over 50%. Current treatments are limited, and resistance to therapy remains a significant clinical obstacle. IsCT1, a membrane-active peptide derived from the venom of the scorpion Opisthacanthus madagascariensis, has shown antitumor effects in various cancer cell lines, including breast cancer and chronic myeloid leukemia. However, its hemolytic action limits its potential therapeutic use. This study aims to assess the antitumor and antiproliferative activities of synthetic peptides derived from IsCT1 (IsCT-P, AC-AFPK-IsCT1, AFPK-IsCT1, AC-KKK-IsCT1, and KKK-IsCT1) in the context of oral squamous cell carcinoma. We evaluated the cytotoxic effects of these peptides on tongue squamous cell carcinoma cells and normal cells, as well as their impact on cell cycle phases, the expression of proliferation markers, modulators of cell death pathways, and mitochondrial potential. Our results indicate that the IsCT1 derivatives IsCT-P and AC-AFPK-IsCT1 possess cytotoxic properties towards squamous cell carcinoma cells, reducing mitochondrial membrane potential and the proliferative index. The treatment of cancer cells with AC-AFPK-IsCT1 led to a positive modulation of pro-apoptotic markers p53 and caspases 3 and 8, a decrease in PCNA and Cyclin D1 expression, and cell cycle arrest in the S phase. Notably, contrary to the parental IsCT1 peptide, AC-AFPK-IsCT1 did not exhibit hemolytic activity or cytotoxicity towards normal cells. Therefore, AC-AFPK-IsCT1 might be a viable therapeutic option for head and neck cancer treatment.

Repeated Sprint Variations According to Circadian Rhythm at Different Menstrual Cycle Phases.

This study assessed the repeated sprint performance in relation to circadian rhythm during different menstrual cycle phases (MCP). Twelve volunteer eumenorrheic women team sport athletes performed 5×6-s cycling sprints in morning (9 am to 10 am) and evening (6 pm to 7 pm) sessions during the mid-follicular (FP, 6th-10th d) and luteal phases (LP, 19th-24th d). Body weight, oral body temperature, resting heart rate and lactate levels together with estradiol, progesterone and cortisol levels were determined before tests. Relative peak and mean power and performance decrements were determined as performance variables and maximum heart rate, lactate and ratings of perceived exertion were determined as physiological variables. Evening body temperatures were significantly higher. Cortisol levels were higher in the morning and in the FP. Resting lactate levels did not vary with MCP or time of day, but a significant MCP x time of day interaction was observed. Body weight showed no change according to time of day and MCP. There was no significant effect of MCP and time of day on performance and physiological variables, in contrast, maximum lactate values were notably higher in the evening. In conclusion, MCP and time of day need not be considered during repeated sprint exercises of eumenorrheic women athletes.

Serum-Free Medium Supplemented with Haematococcus pluvialis Extracts for the Growth of Human MRC-5 Fibroblasts.

Experiments are increasingly performed in vitro; therefore, cell culture technology is essential for scientific progress. Fetal bovine serum (FBS) is a key cell culture supplement providing growth factors, amino acids, and hormones. However, FBS is not readily available on the market, has contamination risks, and has ethical concerns. This study aimed to investigate Haematococcus pluvialis extracts (HE) as a potential substitute for FBS. Therefore, we assessed the effects of HE on cell maintenance, growth, and cycle progression in human lung fibroblasts (MRC-5). Cell progression and monosaccharide, fatty acid, and free amino acid compositions were analyzed using cell cycle analysis, bio-liquid chromatography, gas chromatography, and high-performance liquid chromatography, respectively. The results of nutritional profiles showed that the extracts contained essential amino acids required for synthesizing non-essential amino acids and other metabolic intermediates. Furthermore, most of the components present in HE were consistent with those found in FBS. HE enhanced cell viability and regulated cell cycle phases. Additionally, the interaction between growth factor cocktails and HE significantly improved cell viability, promoted cell cycle progression, and activated key cell cycle regulators, such as cyclin A and cyclin-dependent kinases 1 (CDK1). Our findings suggest that HE have considerable potential to substitute FBS in MRC-5 cell cultures and have functional and ethical advantages.

Exosomal miRNAs Differentiate Chronic Total Occlusion from Acute Myocardial Infarction.

Although coronary artery occlusion can have a negative effect on the myocardium, chronic total occlusion (CTO) exhibits different clinical features from those of acute myocardial infarction (AMI). In this study, we identify the differential associations of exosomal miRNAs with CTO and AMI. Exosomes were isolated from the plasma obtained from coronary arteries of patients undergoing percutaneous coronary intervention to treat CTO (n = 29) and AMI (n = 24), followed by small RNA sequencing, target gene predictions, and functional enrichment analyses. Promising miRNA markers were validated using real-time PCR in 35 CTO, 35 AMI, and 10 normal subjects. A total of 205 miRNAs were detected in all subjects, and 20 and 12 miRNAs were upregulated and downregulated in CTO compared to AMI patients, respectively (|fold change| > 4, FDR q < 0.05). The target genes of miRNAs that were higher in CTO patients were associated with "regulation of cell cycle phase transition", "cell growth", and "apoptosis". The target genes of miRNAs that were lower in CTO patients were enriched in terms such as "muscle cell differentiation", "response to oxygen levels", and "artery morphogenesis". On qRT-PCR analysis, the expression levels of miR-9-5p and miR-127-3p were significantly different between CTO and AMI patients. The miRNA expression levels accurately distinguished CTO from AMI patients with 79% specificity and 97% sensitivity. The miRNA contents of plasma exosomes were significantly different between CTO and AMI patients. The miRNAs may play important roles in CTO and AMI.

Dynamic MRI interpolation in temporal direction using an unsupervised generative model

PurposeCardiac cine magnetic resonance imaging (MRI) is an important tool in assessing dynamic heart function. However, this technique requires long acquisition time and long breath holds, which presents difficulties. The aim of this study is to propose an unsupervised neural network framework that can perform cardiac cine interpolation in time, so that we can increase the temporal resolution of cardiac cine without increasing acquisition time. MethodsIn this study, a subject-specific unsupervised generative neural network is designed to perform temporal interpolation for cardiac cine MRI. The network takes in a 2D latent vector in which each element corresponds to one cardiac phase in the cardiac cycle and then the network outputs the cardiac cine images which are acquired on the scanner. After the training of the generative network, we can interpolate the 2D latent vector and input the interpolated latent vector into the network and the network will output the frame-interpolated cine images. The results of the proposed cine interpolation neural network (CINN) framework are compared quantitatively and qualitatively with other state-of-the-art methods, the ground truth training cine frames, and the ground truth frames removed from the original acquisition. Signal-to-noise ratio (SNR), structural similarity index measures (SSIM), peak signal-to-noise ratio (PSNR), strain analysis, as well as the sharpness calculated using the Tenengrad algorithm were used for image quality assessment. ResultsAs shown quantitatively and qualitatively, the proposed framework learns the generative task well and hence performs the temporal interpolation task well. Furthermore, both quantitative and qualitative comparison studies show the effectiveness of the proposed framework in cardiac cine interpolation in time. ConclusionThe proposed generative model can effectively learn the generative task and perform high quality cardiac cine interpolation in time.

M6A-modified cenRNA stabilizes CENPA to ensure centromere integrity in cancer cells

m6A modification is best known for its critical role in controlling multiple post-transcriptional processes of the mRNAs. Here, we discovered elevated levels of m6A modification on centromeric RNA (cenRNA) in cancerous cells compared with non-cancerous cells. We then identified CENPA, an H3 variant, as an m6A reader of cenRNA. CENPA is localized at centromeres and is essential in preserving centromere integrity and function during mitosis. The m6A-modified cenRNA stabilizes centromeric localization of CENPA in cancer cells during the S phase of the cell cycle. Mutations of CENPA at the Leu61 and the Arg63 or removal of cenRNA m6A modification lead to loss of centromere-bound CENPA during S phase. This in turn results in compromised centromere integrity and abnormal chromosome separation and hinders cancer cell proliferation and tumor growth. Our findings unveil an m6A reading mechanism by CENPA that epigenetically governs centromere integrity in cancer cells, providing potential targets for cancer therapy.