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CO2-based transcritical refrigeration cycles are currently gaining significant research attention, as they offer a viable solution to the use of natural refrigerants (e.g., CO2). However, there are almost no papers that offer an exergoeconomic comparison between the different configurations of these types of systems. Accordingly, the present work deals with a comparative exergoeconomic analysis of four different CO2-based transcritical refrigeration cycles. In addition, the work is complemented by an analysis of the CO2 abatement costs. The influences of the variation of the evaporating temperature, the gas cooler outlet temperature, and the pressure ratio on the exergy efficiency, product cost rate, exergy destruction cost rate, exergoeconomic factor, and CO2 penalty cost rate are compared in detail. The results show that the transcritical cycle with the ejector has the lowest exergetic product cost and a low environmental impact. [ABSTRACT FROM AUTHOR]

Obesity drastically affects maternal health and reproductive outcomes, being often associated with endocrine imbalance, compromised ovarian function, and pregnancy complications. The plastic nature of pregnancy may render the developing fetus particularly vulnerable to oscillations in maternal metabolism, ultimately shaping the health trajectories of the offspring. Presently, we discuss the impact of maternal obesity on decidualisation, a critical step for embryo implantation and placental development. Decidualisation encompasses the differentiation of endometrial stromal cells into specialised decidua. Impaired decidualisation was linked to pregnancy complications, and recent studies suggest that maternal obesity has a detrimental effect on decidualisation. Leptin, an adipokine significantly increased in the circulation of obese women, is known to regulate endometrial function and decidualisation, modulating immune response, angiogenesis, and cell proliferation. Furthermore, hyperleptinaemia in obese mothers was linked to altered leptin signalling in the uterus and compromised endometrial function. In this review, we explore the underlying molecular mechanisms linking altered uterine leptin signalling to impaired decidualisation and early pregnancy complications in obese mothers.

High-grade serous ovarian cancer (HGSOC) is the most lethal form of gynecologic cancer, with limited treatment options and a poor prognosis. Epigenetic factors, such as microRNAs (miRNAs) and DNA methylation, play pivotal roles in cancer progression, yet their specific contributions to HGSOC remain insufficiently understood. In this study, we performed comprehensive high-throughput analyses to identify dysregulated miRNAs in HGSOC and investigate their epigenetic regulation. Analysis of tissue samples from advanced-stage HGSOC patients revealed 20 differentially expressed miRNAs, 11 of which were corroborated via RT-qPCR in patient samples and cancer cell lines. Among these, miR-145-3p was consistently downregulated post-neoadjuvant therapy and was able to distinguish tumoural from control tissues. Further investigation confirmed that DNA methylation controls MIR145 expression. Functional assays showed that overexpression of miR-145-3p significantly reduced cell migration and induced G0/G1 cell cycle arrest by modulating the cyclin D1-CDK4/6 pathway. These findings suggest that miR-145-3p downregulation enhances cell proliferation and motility in HGSOC, implicating its restoration as a potential therapeutic target focused on G1/S phase regulation in the treatment of HGSOC.

The placenta, a pivotal organ in mammalian reproduction, allows nutrient exchange and hormonal signaling between the mother and the developing fetus. Understanding its molecular intricacies is essential for deciphering normal embryonic development and pathological conditions such as tumorigenesis. Here, we explore the multifaceted role of the tumor suppressor BRCA1-associated protein 1 (BAP1) in cancer and placentation. Initially recognized for its tumor-suppressive properties, BAP1 has emerged as a key regulator at the intersection of tumorigenesis and placental development. BAP1 influences crucial cellular processes such as cell death, proliferation, metabolism, and response to hypoxic conditions. By integrating insights from tumor and developmental biology, we illuminate the complex molecular pathways orchestrated by BAP1. This perspective highlights BAP1's significant impact on both cancer and placental development, and suggests novel therapeutic strategies that could improve outcomes for pregnancy disorders and cancer., (© 2024. The Author(s).)

The glycosylphosphatidylinositol (GPI) biosynthetic pathway in the endoplasmic reticulum (ER) is crucial for generating GPI-anchored proteins (GPI-APs), which are translocated to the cell surface and play a vital role in cell signaling and adhesion. This study focuses on two integral components of the GPI pathway, the PIGL and PIGF proteins, and their significance in trophoblast biology. We show that GPI pathway mutations impact on placental development impairing the differentiation of the syncytiotrophoblast (SynT), and especially the SynT-II layer, which is essential for the establishment of the definitive nutrient exchange area within the placental labyrinth. CRISPR/Cas9 knockout of Pigl and Pigf in mouse trophoblast stem cells (mTSCs) confirms the role of these GPI enzymes in syncytiotrophoblast differentiation. Mechanistically, impaired GPI-AP generation induces an excessive unfolded protein response (UPR) in the ER in mTSCs growing in stem cell conditions, akin to what is observed in human preeclampsia. Upon differentiation, the impairment of the GPI pathway hinders the induction of WNT signaling for early SynT-II development. Remarkably, the transcriptomic profile of Pigl- and Pigf-deficient cells separates human patient placental samples into preeclampsia and control groups, suggesting an involvement of Pigl and Pigf in establishing a preeclamptic gene signature. Our study unveils the pivotal role of GPI biosynthesis in early placentation and uncovers a new preeclampsia gene expression profile associated with mutations in the GPI biosynthesis pathway, providing novel molecular insights into placental development with implications for enhanced patient stratification and timely interventions., (© 2024. The Author(s).)

The placenta is a vital organ that regulates nutrient supply to the developing embryo during gestation. In mice, the placenta is composed of trophoblast lineage and mesodermal derivatives, which merge through the chorioallantoic fusion process in a critical event for the progression of placenta development. The trophoblast lineage is derived from self-renewing, multipotent cells known as mouse trophoblast stem cells (mTSCs). These cells are a valuable tool that allows scientists to comprehend the signals regulating major placental cell types' self-renewal and differentiation capacity. Recent advances in CRISPR-Cas9 genome editing applied in mTSCs have provided novel insights into the molecular networks involved in placentation. Here, we present a comprehensive CRISPR activation (CRISPRa) protocol based on the CRISPR/gRNA-directed synergistic activation mediator (SAM) method to overexpress specific target genes in mTSCs., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The placenta is the organ that dictates the reproductive outcome of mammalian pregnancy by supplying nutrients and oxygen to the developing fetus to sustain its normal growth. During early mammalian development, trophoblast cells are the earliest cell type to differentiate with multipotent capacity to generate the trophoblast components of the placenta. The isolation and use of mouse trophoblast stem cells (mTSCs) to model in vitro trophoblast differentiation, in combination with CRISPR/Cas9 genome editing technology, has provided tremendous insight into the molecular mechanisms governing early mouse placentation. By knocking out a specific gene of interest in mTSCs, researchers are shedding light onto the molecular pathways involved in normal placental development and pregnancy disorders associated with abnormal placentation. In this chapter, we provide a detailed protocol for the genetic modification of mTSCs by using CRISPR/Cas9 genome editing system., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Global polystyrene (PS) production has been influenced by the lightness and heat resistance this material offers in different applications, such as construction and packaging. However, population growth and the lack of PS recycling lead to a large waste generation, affecting the environment. Pyrolysis has been recognized as an effective recycling method, converting PS waste into valuable products in the chemical industry. The present work addresses a systematic, bibliometric, and statistical analysis of results carried out from 2015 to 2022, making an extensive critique of the most influential operation parameters in the thermo-catalytic pyrolysis of PS and its waste. The systematic study showed that the conversion of PS into a liquid with high aromatic content (84.75% of styrene) can be achieved by pyrolysis. Discussion of PS as fuel is described compared to commercial fuels. In addition, PS favors the production of liquid fuel when subjected to co-pyrolysis with biomass, improving its properties such as viscosity and energy content. A statistical analysis of the data compilation was also discussed, evaluating the influence of temperature, reactor design, and catalysts on product yield.

Evolutionary dynamics allows us to understand many changes happening in a broad variety of biological systems, ranging from individuals to complete ecosystems. It is also behind a number of remarkable organizational changes that happen during the natural history of cancers. These reflect tumour heterogeneity, which is present at all cellular levels, including the genome, proteome and phenome, shaping its development and interrelation with its environment. An intriguing observation in different cohorts of oncological patients is that tumours exhibit an increased proliferation as the disease progresses, while the timescales involved are apparently too short for the fixation of sufficient driver mutations to promote explosive growth. Here, we discuss how phenotypic plasticity, emerging from a single genotype, may play a key role and provide a ground for a continuous acceleration of the proliferation rate of clonal populations with time. We address this question by combining the analysis of real-time growth of non-small-cell lung carcinoma cells (N-H460) together with stochastic and deterministic mathematical models that capture proliferation trait heterogeneity in clonal populations to elucidate the contribution of phenotypic transitions on tumour growth dynamics., (© 2022. The Author(s), under exclusive licence to Society for Mathematical Biology.)

The mechanism governing the transition of human embryonic stem cells (hESCs) toward differentiated cells is only partially understood. To explore this transition, the activity and expression of the ubiquitous phosphatidylinositol 3-kinase (PI3Kα and PI3Kβ) were modulated in primed hESCs. The study reports a pathway that dismantles the restraint imposed by the EZH2 polycomb repressor on an essential stemness gene, NODAL, and on transcription factors required to trigger primitive streak formation. The primitive streak is the site where gastrulation begins to give rise to the three embryonic cell layers from which all human tissues derive. The pathway involves a PI3Kβ non-catalytic action that controls nuclear/active RAC1 levels, activation of JNK (Jun N-terminal kinase) and nuclear β-catenin accumulation. β-Catenin deposition at promoters triggers release of the EZH2 repressor, permitting stemness maintenance (through control of NODAL) and correct differentiation by allowing primitive streak master gene expression. PI3Kβ epigenetic control of EZH2/β-catenin might be modulated to direct stem cell differentiation., Competing Interests: Conflict of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Transient receptor potential (TRP) channels play prominent roles in ion homeostasis by their ability to control cation influx. Mouse placentation is governed by the processes of trophoblast proliferation, invasion, differentiation, and fusion, all of which require calcium signaling. Although certain TRP channels have been shown to contribute to maternal-fetal transport of magnesium and calcium, a role for TRP channels in specific trophoblast functions has been disregarded. Using qRT-PCR and in situ hybridisation, the spatio-temporal expression pattern of TRP channels in the mouse placenta across gestation (E10.5-E18.5) was assessed. Prominent expression was observed for Trpv2, Trpm6, and Trpm7. Calcium microfluorimetry in primary trophoblast cells isolated at E14.5 of gestation further revealed the functional activity of TRPV2 and TRPM7. Finally, comparing TRP channels expression in mouse trophoblast stem cells (mTSCs) and mouse embryonic stem cells (mESC) confirmed the specific expression of TRPV2 during placental development. Moreover, TRP channel expression was similar in mTSCs compared to primary trophoblasts and validate mTSC as a model to study TRP channels in placental development. Collectivity, our results identify a specific spatio-temporal TRP channel expression pattern in trophoblasts, suggesting a possible involvement in regulating the process of placentation.

Purpose: The ergogenic effect of caffeine on exercise of maximum intensity has been well established. However, there is controversy regarding the effect of caffeine on shifting substrate oxidation at submaximal exercise. The aim of this study was to investigate the effect of acute caffeine ingestion on whole-body substrate oxidation during 1 h of cycling at the intensity that elicits maximal fat oxidation (Fatmax)., Methods: In a double-blind, randomized, and counterbalanced experiment, 12 healthy participants (VO 2max  = 50.7 ± 12.1 mL/kg/min) performed two acute experimental trials after ingesting either caffeine (3 mg/kg) or a placebo (cellulose). The trials consisted of 1 h of continuous cycling at Fatmax. Energy expenditure, fat oxidation rate, and carbohydrate oxidation rate were continuously measured by indirect calorimetry., Results: In comparison to the placebo, caffeine increased the amount of fat oxidized during the trial (19.4 ± 7.7 vs 24.7 ± 9.6 g, respectively; P = 0.04) and decreased the amount of carbohydrate oxidized (94.6 ± 30.9 vs 73.8 ± 32.4 g; P = 0.01) and the mean self-perception of fatigue (Borg scale = 11 ± 2 vs 10 ± 2 arbitrary units; P = 0.05). In contrast, caffeine did not modify total energy expenditure (placebo = 543 ± 175; caffeine = 559 ± 170 kcal; P = 0.60) or mean heart rate (125 ± 13 and 127 ± 9 beats/min; P = 0.30) during exercise. Before exercise, caffeine increased systolic and diastolic blood pressure whilst it increased the feelings of nervousness and vigour after exercise (P < 0.05)., Conclusion: These results suggest that a moderate dose of caffeine (3 mg/kg) increases the amount of fat oxidized during 1 h of cycling at Fatmax. Thus, caffeine might be used as an effective strategy to enhance body fat utilization during submaximal exercise. The occurrence of several side effects should be taken into account when using caffeine to reduce body fat in populations with hypertension or high sensitivity to caffeine.

Aim: To analyze the relationship between measurements of global heterogeneity, obtained from 18 F-FDG PET/CT, with biological variables, and their predictive and prognostic role in patients with locally advanced breast cancer (LABC)., Material and Methods: 68 patients from a multicenter and prospective study, with LABC and a baseline 18 F-FDG PET/CT were included. Immunohistochemical profile [estrogen receptors (ER) and progesterone receptors (PR), expression of the HER-2 oncogene, Ki-67 proliferation index and tumor histological grade], response to neoadjuvant chemotherapy (NC), overall survival (OS) and disease-free survival (DFS) were obtained as clinical variables. Three-dimensional segmentation of the lesions, providing SUV, volumetric [metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] and global heterogeneity variables [coefficient of variation (COV) and SUVmean/SUVmax ratio], as well as sphericity was performed. The correlation between the results obtained with the immunohistochemical profile, the response to NC and survival was also analyzed., Results: Of the patients included, 62 received NC. Only 18 responded. 13 patients relapsed and 11 died during follow-up. ER negative tumors had a lower COV (p=0.018) as well as those with high Ki-67 (p=0.001) and high risk phenotype (p=0.033) compared to the rest. No PET variable showed association with the response to NC nor OS. There was an inverse relationship between sphericity with DFS (p=0.041), so, for every tenth that sphericity increases, the risk of recurrence decreases by 37%., Conclusions: Breast tumors in our LABC dataset behaved as homogeneous and spherical lesions. Larger volumes were associated with a lower sphericity. Global heterogeneity variables and sphericity do not seem to have a predictive role in response to NC nor in OS. More spherical tumors with less variation in gray intensity between voxels showed a lower risk of recurrence., (Copyright © 2019 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.)

Studies suggest that placental nutrient supply adapts according to fetal demands. However, signaling events underlying placental adaptations remain unknown. Here we demonstrate that phosphoinositide 3-kinase p110α in the fetus and the trophoblast interplay to regulate placental nutrient supply and fetal growth. Complete loss of fetal p110α caused embryonic death, whilst heterozygous loss resulted in fetal growth restriction and impaired placental formation and nutrient transport. Loss of trophoblast p110α resulted in viable fetuses, abnormal placental development and a failure of the placenta to transport sufficient nutrients to match fetal demands for growth. Using RNA-seq we identified genes downstream of p110α in the trophoblast that are important in adapting placental phenotype. Using CRISPR/Cas9 we showed loss of p110α differentially affects gene expression in trophoblast and embryonic stem cells. Our findings reveal important, but distinct roles for p110α in the different compartments of the conceptus, which control fetal resource acquisition and growth., Competing Interests: JL, VP, JK, LK, WC, AA, IG, EF, BL, MH, IS, MC, AS No competing interests declared, (© 2019, López-Tello et al.)

Background and Purpose: Multifocal glioblastomas (ie, glioblastomas with multiple foci, unconnected in postcontrast pretreatment T1-weighted images) represent a challenge in clinical practice due to their poor prognosis. We wished to obtain imaging biomarkers with prognostic value that have not been found previously., Materials and Methods: A retrospective review of 1155 patients with glioblastomas from 10 local institutions during 2006-2017 provided 97 patients satisfying the inclusion criteria of the study and classified as having multifocal glioblastomas. Tumors were segmented and morphologic features were computed using different methodologies: 1) measured on the largest focus, 2) aggregating the different foci as a whole, and 3) recording the extreme value obtained for each focus. Kaplan-Meier, Cox proportional hazards, correlations, and Harrell concordance indices (c-indices) were used for the statistical analysis., Results: Age ( P < .001, hazard ratio = 2.11, c-index = 0.705), surgery ( P < .001, hazard ratio = 2.04, c-index = 0.712), contrast-enhancing rim width ( P < .001, hazard ratio = 2.15, c-index = 0.704), and surface regularity ( P = .021, hazard ratio = 1.66, c-index = 0.639) measured on the largest focus were significant independent predictors of survival. Maximum contrast-enhancing rim width ( P = .002, hazard ratio = 2.05, c-index = 0.668) and minimal surface regularity ( P = .036, hazard ratio = 1.64, c-index = 0.600) were also significant. A multivariate model using age, surgery, and contrast-enhancing rim width measured on the largest foci classified multifocal glioblastomas into groups with different outcomes ( P < .001, hazard ratio = 3.00, c-index = 0.853, median survival difference = 10.55 months). Moreover, quartiles with the highest and lowest individual prognostic scores based on the focus with the largest volume and surgery were identified as extreme groups in terms of survival ( P < .001, hazard ratio = 18.67, c-index = 0.967)., Conclusions: A prognostic model incorporating imaging findings on pretreatment postcontrast T1-weighted MRI classified patients with glioblastoma into different prognostic groups., (© 2019 by American Journal of Neuroradiology.)

A SSW/Al-Cu formed from an industrial solid waste and Al-Cu Nps are utilized for the removal of fluoride from aqueous solutions. The SSW/Al-Cu was obtained by a chemical reduction method. The SSW/Al-Cu was characterized by TEM, SEM, FT-IR, XRD, BET, and pH zpc techniques. The Nps were formed as bimetallic oxides and deposited in the form of spheroidal particles forming agglomerations. The sizes of these particles range from 1 to 3 nm. The surface area and average pore width of SSW/Al-Cu were 2.99 m 2 /g and 17.09 nm, respectively. The adsorption kinetics were better described using the second-order model, pointing to chemical adsorption with an equilibrium time of 540 min. The thermodynamic parameters obtained here confirm the spontaneous and endothermic nature of the process. The percentage of fluoride removal was 89.5% using the four-bladed disk turbine, and computational fluid dynamics (CFD) modeling demonstrated that using the four-bladed disk turbine helped improve the fluoride removal process. The maximum adsorption capacity was 3.99 mg/g. The Langmuir-Freundlich model best describes the adsorption process, which occurred by a combination of mechanisms, such as electrostatic interactions between the ions involved in the process. This study proves that the chemical modification of this waste solid created an efficient bimetallic nanomaterial for fluoride removal. Furthermore, the method of preparation of these nanocomposites is quite scalable.

Low grade gliomas (LGGs) are infiltrative and incurable primary brain tumours with typically slow evolution. These tumours usually occur in young and otherwise healthy patients, bringing controversies in treatment planning since aggressive treatment may lead to undesirable side effects. Thus, for management decisions it would be valuable to obtain early estimates of LGG growth potential. Here we propose a simple mathematical model of LGG growth and its response to chemotherapy which allows the growth of LGGs to be described in real patients. The model predicts, and our clinical data confirms, that the speed of response to chemotherapy is related to tumour aggressiveness. Moreover, we provide a formula for the time to radiological progression, which can be possibly used as a measure of tumour aggressiveness. Finally, we suggest that the response to a few chemotherapy cycles upon diagnosis might be used to predict tumour growth and to guide therapeutical actions on the basis of the findings., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Gene expression data are accumulating exponentially in public repositories. Reanalysis and integration of themed collections from these studies may provide new insights, but requires further human curation. Here we report a crowdsourcing project to annotate and reanalyse a large number of gene expression profiles from Gene Expression Omnibus (GEO). Through a massive open online course on Coursera, over 70 participants from over 25 countries identify and annotate 2,460 single-gene perturbation signatures, 839 disease versus normal signatures, and 906 drug perturbation signatures. All these signatures are unique and are manually validated for quality. Global analysis of these signatures confirms known associations and identifies novel associations between genes, diseases and drugs. The manually curated signatures are used as a training set to develop classifiers for extracting similar signatures from the entire GEO repository. We develop a web portal to serve these signatures for query, download and visualization.

The nuclear envelope (NE) forms a barrier between the nucleus and the cytosol that preserves genomic integrity. The nuclear lamina and nuclear pore complexes (NPCs) are NE components that regulate nuclear events through interaction with other proteins and DNA. Defects in the nuclear lamina are associated with the development of laminopathies. As cells depleted of phosphoinositide 3-kinase beta (PI3Kβ) showed an aberrant nuclear morphology, we studied the contribution of PI3Kβ to maintenance of NE integrity. pik3cb depletion reduced the nuclear membrane tension, triggered formation of areas of lipid bilayer/lamina discontinuity, and impaired NPC assembly. We show that one mechanism for PI3Kβ regulation of NE/NPC integrity is its association with RCC1 (regulator of chromosome condensation 1), the activator of nuclear Ran GTPase. PI3Kβ controls RCC1 binding to chromatin and, in turn, Ran activation. These findings suggest that PI3Kβ regulates the nuclear envelope through upstream regulation of RCC1 and Ran., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)