bluuebunny/crossref_metadata_2025 huggingface dataset:
Wellbeing Forecasting in Postpartum Anemia Patients
Authors: Susič David , Bombač Tavčar Lea , Lučovnik Miha , Hrobat Hana , Gornik Lea , Gradišek Anton
Published: June 2023

Postpartum anemia is a very common maternal health problem and remains a persistent public health issue globally. It negatively affects maternal mood and could lead to depression, increased fatigue, and decreased cognitive abilities. It can and should be treated by restoring iron stores. However, in most health systems, there is typically a six-week gap between birth and the follow-up postpartum visit. Risks of postpartum maternal complications are usually assessed shortly after birth by clinicians intuitively, taking into account psychosocial and physical factors, such as the presence of anemia and the type of iron supplementation. In this paper, we investigate the possibility of using machine-learning algorithms to more reliably forecast three parameters related to patient wellbeing, namely depression (measured by Edinburgh Postnatal Depression Scale—EPDS), overall tiredness, and physical tiredness (both measured by Multidimensional Fatigue Inventory—MFI). Data from 261 patients were used to train the forecasting models for each of the three parameters, and they outperformed the baseline models that always predicted the mean values of the training data. The mean average error of the elastic net regression model for predicting the EPDS score (with values ranging from 0 to 19) was 2.3 and outperformed the baseline, which already hints at the clinical usefulness of using such a model. We further investigated what features are the most important for this prediction, where the EDPS score and both tiredness indexes at birth turned out to be by far the most prominent prediction features. Our study indicates that the machine-learning model approach has the potential for use in clinical practice to predict the onset of depression and severe fatigue in anemic patients postpartum and potentially improve the detection and management of postpartum depression and fatigue.
Work–Family Conflict and Mental Health among Chinese Female Healthcare Workers during the COVID-19 Pandemic: The Moderating Effects of Resilience
Authors: Liu Zixiao , Hong Liu
Published: June 2023

(1) Background: The mental health of female healthcare workers is at greater risk during the COVID-19 pandemic due to increased psychological stress and heightened work–family conflict. This study investigated whether resilience, as a protective factor for mental health, can safeguard the well-being of female healthcare workers. This study assessed the mental health of female healthcare workers (n = 431) from a small inland city in Central China, explored the impact of work–family conflict on their mental health, and examined the moderating role of resilience. (2) Methods: The main variables were measured using standard tools administered via an online survey. A one-sample t-test, ANOVA, Pearson correlation analysis, and multiple regression were performed with SPSS. A simple slope test was conducted based on the multiple regression results. (3) Results: The analysis revealed that the mental health level of the surveyed female healthcare workers was significantly lower than the national norm (t = 16.36, p < 0.001). Work–family conflict had a significant negative impact on mental health (β = 0.39, p < 0.001), while the interaction effect of resilience and work–family conflict was significant (β = −0.13, p < 0.05), suggesting a moderating effect. (4) Conclusions: Female healthcare workers exhibited poor mental health during the COVID-19 pandemic, but resilience remained a protective factor, mitigating the negative impact of work–family conflict on female healthcare workers’ mental health.
Effects of Nursing Work Environment, Need Satisfaction, and Depression on Turnover Intention in Korea
Authors: Shin Sun-Hwa , Baek On-Jeon , Lee Eun-Hye
Published: June 2023

This study examined the effects of the nursing work environment, need satisfaction, and depression on turnover intention in South Korean nurses through a mediating model. This study was a descriptive cross-sectional research study and was conducted through an online questionnaire. A total of 248 nurses were recruited for this study. Data were collected in August 2022. Participants were invited to complete self-reported questionnaires that measure nursing work environment, need satisfaction, depression, turnover intention, and demographic information. The data obtained were analyzed using the dual mediation model applying the PROCESS macro (Model 6). This study analyzed the direct effects of the nursing work environment on need satisfaction, depression, and turnover intention. The nursing work environment also had indirect effects on their turnover intention via need satisfaction and depression. The mediating effect of need satisfaction, which affects the turnover intention by increasing the satisfaction of the nursing work environment, was found to be the greatest. It has been shown that the more positive a nurse’s experience of the nursing work environment, the higher the nurse’s need satisfaction. According to the study results, the increase in nurses’ need satisfaction greatly contributes to the decrease in depression and turnover intention. Therefore, active efforts should be made to improve the nursing work environment to fulfill basic needs.
Water-Saving Technologies in Galapagos Agriculture: A Step towards Sustainability
Authors: Jaramillo Díaz Patricia , Calle-Loor Anna , Velasco Nicolás , Cevallos David
Published: June 2023

Water scarcity and salinity pose significant challenges for agriculture in the Galapagos Islands, severely limiting crop yields needed to sustainably meet the growing demands of the human population in the archipelago. To address this issue, environmentally friendly water-saving technologies such as Hydrogel and Groasis Growboxx were considered to be potential solutions. This study focused on evaluating the effectiveness of Hydrogel application on five crops: Broccoli (Brassica oleracea), Cucumber (Cucumis melo), Pepper (Capsicum annuum), Tomato (Solanum lycopersicum), and Watermelon (Citrullus lanatus), from 2017 to 2018. The experiment stopped due to the pandemic in 2019–2020. When the study continued in 2021, Growboxx® was introduced as a treatment for Pepper and Tomato. This study revealed that the application of Hydrogel resulted in enhanced yields, with the degree of improvement varying across different crops and cultivation periods. Notably, when comparing Hydrogel and Growboxx treatments, differences of up to 30% in fruit weight were observed. However, it is important to note that these results can vary in different environments. For example, in Tomato cultivation, Growboxx exhibited 10% higher fruit weight in San Cristobal compared to Santa Cruz Island. Our findings provide valuable insights for stakeholders in the Galapagos Islands, offering crop-specific guidance to support informed decisions on adopting the most appropriate technologies for their farms.
Dynamic Assimilation of Deep Learning Predictions to a Process-Based Water Budget
Authors: Martin Nick
Published: June 2023

A three-step data assimilation (DA) of deep learning (DL) predictions to a process-based water budget is developed and applied to produce an active, operational water balance for groundwater management. In the first step, an existing water budget model provides forward model predictions of aquifer storage from meteorological observations, estimates of pumping and diversion discharge, and estimates of recharge. A Kalman filter DA approach is the second step and generates updated storage volumes by combining a long short-term memory (LSTM) network, a DL method, and predicted “measurements” with forward model predictions. The third “correction” step uses modified recharge and pumping, adjusted to account for the difference between Kalman update storage and forward model predicted storage, in forward model re-simulation to approximate updated storage volume. Use of modified inputs in the correction provides a mass-conservative water budget framework that leverages DL predictions. LSTM predictor “measurements” primarily represent missing observations due to missing or malfunctioning equipment. Pumping and recharge inputs are uncertain and unobserved in the study region and can be adjusted without contradicting measurements. Because DL requires clean and certain data for learning, a common-sense baseline facilitates interpretation of LSTM generalization skill and accounts for feature and outcome uncertainty when sufficient target data are available. DA, in contrast to DL, provides for explicit uncertainty analysis through an observation error model, which allows the integrated approach to address uncertainty impacts from an LSTM predictor developed from limited outcome observations.
Use of Mixed Methods in the Science of Hydrological Extremes: What Are Their Contributions?
Authors: Kabo Raymond , Bourgault Marc-André , Bissonnette Jean François , Barrette Nathalie , Tanguay Louis
Published: June 2023

Research in hydrological sciences is constantly evolving to provide adequate answers to address various water-related issues. Methodological approaches inspired by mathematical and physical sciences have shaped hydrological sciences from its inceptions to the present day. Nowadays, as a better understanding of the social consequences of extreme meteorological events and of the population’s ability to adapt to these becomes increasingly necessary, hydrological sciences have begun to integrate knowledge from social sciences. Such knowledge allows for the study of complex social-ecological realities surrounding hydrological phenomena, such as citizens’ perception of water resources, as well as individual and collective behaviors related to water management. Using a mixed methods approach to combine quantitative and qualitative approaches has thus become necessary to understand the complexity of hydrological phenomena and propose adequate solutions for their management. In this paper, we detail how mixed methods can be used to research flood hydrology and low-flow conditions, as well as in the management of these hydrological extremes, through the analysis of case studies. We frame our analysis within the three paradigms (positivism, post-positivism, and constructivism) and four research designs (triangulation, complementary, explanatory, and exploratory) that guide research in hydrology. We show that mixed methods can notably contribute to the densification of data on extreme flood events to help reduce forecasting uncertainties, to the production of knowledge on low-flow hydrological states that are insufficiently documented, and to improving participatory decision making in water management and in handling extreme hydrological events.
Follicular Lymphoma Microenvironment Traits Associated with Event-Free Survival
Authors: Tumedei Maria Maddalena , Piccinini Filippo , Azzali Irene , Pirini Francesca , Bravaccini Sara , De Matteis Serena , Agostinelli Claudio , Castellani Gastone , Zanoni Michele , Cortesi Michela , Vergani Barbara , Leone Biagio Eugenio , Righi Simona , Gazzola Anna , Casadei Beatrice , Gentilini Davide , Calzari Luciano , Limarzi Francesco , Sabattini Elena , Pession Andrea , Tazzari Marcella , Bertuzzi Clara
Published: June 2023

The majority of patients with Follicular Lymphoma (FL) experience subsequent phases of remission and relapse, making the disease “virtually” incurable. To predict the outcome of FL patients at diagnosis, various clinical-based prognostic scores have been proposed; nonetheless, they continue to fail for a subset of patients. Gene expression profiling has highlighted the pivotal role of the tumor microenvironment (TME) in the FL prognosis; nevertheless, there is still a need to standardize the assessment of immune-infiltrating cells for the prognostic classification of patients with early or late progressing disease. We studied a retrospective cohort of 49 FL lymph node biopsies at the time of the initial diagnosis using pathologist-guided analysis on whole slide images, and we characterized the immune repertoire for both quantity and distribution (intrafollicular, IF and extrafollicular, EF) of cell subsets in relation to clinical outcome. We looked for the natural killer (CD56), T lymphocyte (CD8, CD4, PD1) and macrophage (CD68, CD163, MA4A4A)-associated markers. High CD163/CD8 EF ratios and high CD56/MS4A4A EF ratios, according to Kaplan–Meier estimates were linked with shorter EFS (event-free survival), with the former being the only one associated with POD24. In contrast to IF CD68+ cells, which represent a more homogeneous population, higher in non-progressing patients, EF CD68+ macrophages did not stratify according to survival. We also identify distinctive MS4A4A+CD163-macrophage populations with different prognostic weights. Enlarging the macrophage characterization and combining it with a lymphoid marker in the rituximab era, in our opinion, may enable prognostic stratification for low-/high-grade FL patients beyond POD24. These findings warrant validation across larger FL cohorts.
Dimethyl Fumarate and Intestine: From Main Suspect to Potential Ally against Gut Disorders
Authors: Manai Federico , Zanoletti Lisa , Arfini Davide , Micco Simone Giorgio De , Gjyzeli Arolda , Comincini Sergio , Amadio Marialaura
Published: June 2023

Dimethyl fumarate (DMF) is a well-characterized molecule that exhibits immuno-modulatory, anti-inflammatory, and antioxidant properties and that is currently approved for the treatment of psoriasis and multiple sclerosis. Due to its Nrf2-dependent and independent mechanisms of action, DMF has a therapeutic potential much broader than expected. In this comprehensive review, we discuss the state-of-the-art and future perspectives regarding the potential repurposing of DMF in the context of chronic inflammatory diseases of the intestine, such as inflammatory bowel disorders (i.e., Crohn’s disease and ulcerative colitis) and celiac disease. DMF’s mechanisms of action, as well as an exhaustive analysis of the in vitro/in vivo evidence of its beneficial effects on the intestine and the gut microbiota, together with observational studies on multiple sclerosis patients, are here reported. Based on the collected evidence, we highlight the new potential applications of this molecule in the context of inflammatory and immune-mediated intestinal diseases.
Interactome of Long Non-Coding RNAs: Transcriptomic Expression Patterns and Shaping Cancer Cell Phenotypes
Authors: DeSouza Nicole R. , Quaranto Danielle , Carnazza Michelle , Jarboe Tara , Tiwari Raj K. , Geliebter Jan
Published: June 2023

RNA biology has gained extensive recognition in the last two decades due to the identification of novel transcriptomic elements and molecular functions. Cancer arises, in part, due to the accumulation of mutations that greatly contribute to genomic instability. However, the identification of differential gene expression patterns of wild-type loci has exceeded the boundaries of mutational study and has significantly contributed to the identification of molecular mechanisms that drive carcinogenic transformation. Non-coding RNA molecules have provided a novel avenue of exploration, providing additional routes for evaluating genomic and epigenomic regulation. Of particular focus, long non-coding RNA molecule expression has been demonstrated to govern and direct cellular activity, thus evidencing a correlation between aberrant long non-coding RNA expression and the pathological transformation of cells. lncRNA classification, structure, function, and therapeutic utilization have expanded cancer studies and molecular targeting, and understanding the lncRNA interactome aids in defining the unique transcriptomic signatures of cancer cell phenotypes.
Neonatal Meningitis-Causing Escherichia coli Induces Microglia Activation which Acts as a Double-Edged Sword in Bacterial Meningitis
Authors: Su Yingying , Ma Guozhen , Zheng Yangyang , Qin Jingliang , Li Xiaoya , Ge Qianwen , Sun Hao , Liu Bin
Published: June 2023

Bacterial meningitis is a devastating disease occurring worldwide, with up to half of survivors left with permanent neurological sequelae. Neonatal meningitis-causing Escherichia coli (NMEC) is the most common Gram-negative bacillary organism that causes meningitis, particularly during the neonatal period. Here, RNA-seq transcriptional profiles of microglia in response to NMEC infection show that microglia are activated to produce inflammatory factors. In addition, we found that the secretion of inflammatory factors is a double-edged sword that promotes polymorphonuclear neutrophil (PMN) recruitment to the brain to clear the pathogens but, at the same time, induces neuronal damage, which may be related to the neurological sequelae. New neuroprotective therapeutic strategies must be developed for the treatment of acute bacterial meningitis. We found that transforming growth factor-β (TGF-β) may be a strong candidate in the treatment of acute bacterial meningitis, as it shows a therapeutic effect on bacterial-meningitis-induced brain damage. Prevention of disease and early initiation of the appropriate treatment in patients with suspected or proven bacterial meningitis are the key factors in reducing morbidity and mortality. Novel antibiotic and adjuvant treatment strategies must be developed, and the main goal for new therapies will be dampening the inflammatory response. Based on this view, our findings may help develop novel strategies for bacterial meningitis treatment.
Role of Telomeres and Telomerase in Cancer and Aging
Authors: Saretzki Gabriele
Published: June 2023

Seventeen papers published in 2019 and early 2020 demonstrate the ongoing interest and research concerning telomeres and telomerase in aging and cancer [...]
Upregulated Expression of ERBB2/HER2 in Multiple Myeloma as a Predictor of Poor Survival Outcomes
Authors: Uckun Fatih M. , Qazi Sanjive
Published: June 2023

The main goal of the present study was to examine if the RNA-sequencing (RNAseq)-based ERBB2/HER2 expression level in malignant plasma cells from multiple myeloma (MM) patients has clinical significance for treatment outcomes and survival. We examined the relationship between the RNAseq-based ERBB2 messenger ribonucleic acid (mRNA) levels in malignant plasma cells and survival outcomes in 787 MM patients treated on contemporary standard regimens. ERBB2 was expressed at significantly higher levels than ERBB1 as well as ERBB3 across all three stages of the disease. Upregulated expression of ERBB2 mRNA in MM cells was correlated with amplified expression of mRNAs for transcription factors (TF) that recognize the ERBB2 gene promoter sites. Patients with higher levels of ERBB2 mRNA in their malignant plasma cells experienced significantly increased cancer mortality, shorter progression-free survival, and worse overall survival than other patients. The adverse impact of high ERBB2 expression on patient survival outcomes remained significant in multivariate Cox proportional hazards models that accounted for the effects of other prognostic factors. To the best of our knowledge, this is the first demonstration of an adverse prognostic impact of high-level ERBB2 expression in MM patients. Our results encourage further evaluation of the prognostic significance of high-level ERBB2 mRNA expression and the clinical potential of ERBB2-targeting therapeutics as personalized medicines to overcome cancer drug resistance in high-risk as well as relapsed/refractory MM.
Molecular Mechanisms Driven by MT4-MMP in Cancer Progression
Authors: Muñoz-Sáez Emma , Moracho Natalia , Learte Ana I. R. , Collignon Alice , Arroyo Alicia G. , Noel Agnés , Sounni Nor Eddine , Sánchez-Camacho Cristina
Published: June 2023

MT4-MMP (or MMP-17) belongs to the membrane-type matrix metalloproteinases (MT-MMPs), a distinct subset of the MMP family that is anchored to the cell surface, in this case by a glycosylphosphatidylinositol (GPI) motif. Its expression in a variety of cancers is well documented. However, the molecular mechanisms by which MT4-MMP contributes to tumor development need further investigation. In this review, we aim to summarize the contribution of MT4-MMP in tumorigenesis, focusing on the molecular mechanisms triggered by the enzyme in tumor cell migration, invasiveness, and proliferation, in the tumor vasculature and microenvironment, as well as during metastasis. In particular, we highlight the putative substrates processed and signaling cascades activated by MT4-MMP that may underlie these malignancy processes and compare this with what is known about its role during embryonic development. Finally, MT4-MMP is a relevant biomarker of malignancy that can be used for monitoring cancer progression in patients as well as a potential target for future therapeutic drug development.
Oligo-FISH of Populus simonii Pachytene Chromosomes Improves Karyotyping and Genome Assembly
Authors: Zhao Yilian , Liu Guangxin , Wang Ziyue , Ning Yihang , Ni Runxin , Xi Mengli
Published: June 2023

Poplar was one of the first woody species whose individual chromosomes could be identified using chromosome specific painting probes. Nevertheless, high-resolution karyotype construction remains a challenge. Here, we developed a karyotype based on the meiotic pachytene chromosome of Populus simonii which is a Chinese native species with many excellent traits. This karyotype was anchored by oligonucleotide (oligo)-based chromosome specific painting probes, a centromere-specific repeat (Ps34), ribosomal DNA, and telomeric DNA. We updated the known karyotype formula for P. simonii to 2n = 2x = 38 = 26m + 8st + 4t and the karyotype was 2C. The fluorescence in situ hybridization (FISH) results revealed some errors in the current P. simonii genome assembly. The 45S rDNA loci were located at the end of the short arm of chromosomes 8 and 14 by FISH. However, they were assembled on pseudochromosomes 8 and 15. In addition, the Ps34 loci were distributed in every centromere of the P. simonii chromosome in the FISH results, but they were only found to be present in pseudochromosomes 1, 3, 6, 10, 16, 17, 18, and 19. Our results reveal that pachytene chromosomes oligo-FISH is a powerful tool for constructing high-resolution karyotypes and improving the quality of genome assembly.
IL-7 Deficiency Exacerbates Atopic Dermatitis in NC/Nga Mice
Authors: Park Hyun Jung , Lee Sung Won , Van Kaer Luc , Lee Myeong Sup , Hong Seokmann
Published: June 2023

Interleukin-7 (IL-7) plays a vital role in the homeostasis of CD4+ and CD8+ T cells. Although IL-7 has been implicated in T helper (Th)1- and Th17-mediated autoinflammatory diseases, its role in Th2-type allergic disorders, such as atopic dermatitis (AD), remains unclear. Thus, to elucidate the effects of IL-7 deficiency on AD development, we generated IL-7-deficient AD-prone mice by backcrossing IL-7 knockout (KO) B6 mice onto the NC/Nga (NC) mouse strain, a model for human AD. As expected, IL-7 KO NC mice displayed defective development of conventional CD4+ and CD8+ T cells compared with wild type (WT) NC mice. However, IL-7 KO NC mice presented with enhanced AD clinical scores, IgE hyperproduction, and increased epidermal thickness compared with WT NC mice. Moreover, IL-7 deficiency decreased Th1, Th17, and IFN-γ-producing CD8+ T cells but increased Th2 cells in the spleen of NC mice, indicating that a reduced Th1/Th2 ratio correlates with severity of AD pathogenesis. Furthermore, significantly more basophils and mast cells infiltrated the skin lesions of IL-7 KO NC mice. Taken together, our findings suggest that IL-7 could be a useful therapeutic target for treating Th2-mediated skin inflammations, such as AD.
Relationship between GABA-Ergic System and the Expression of Mephedrone-Induced Reward in Rats—Behavioral, Chromatographic and In Vivo Imaging Study
Authors: Wronikowska-Denysiuk Olga , Michalak Agnieszka , Pankowska Anna , Kurach Łukasz , Kozioł Paulina , Łazorczyk Artur , Kochalska Katarzyna , Targowska-Duda Katarzyna , Boguszewska-Czubara Anna , Budzyńska Barbara
Published: June 2023

Mephedrone is a psychoactive drug that increases dopamine, serotonin and noradrenaline levels in the central nervous system via interaction with transporters or monoamines. The aim of the presented study was to assess the role of the GABA-ergic system in the expression of mephedrone-induced reward. For this purpose, we conducted (a) a behavioral evaluation of the impact of baclofen (a GABAB receptors agonist) and GS39783 (a positive allosteric modulator of GABAB receptors) on the expression of mephedrone-induced conditioned place preference (CPP) in rats, (b) an ex vivo chromatographic determination of the GABA level in the hippocampi of rats subchronically treated with mephedrone and (c) an in vivo evaluation of GABA hippocampal concentration in rats subchronically administered with mephedrone using magnetic resonance spectroscopy (MRS). The results show that GS39783 (but not baclofen) blocked the expression of CPP induced by (20 mg/kg of) mephedrone. The behavioral effect was consistent with chromatographic analysis, which showed that mephedrone (5 and 20 mg/kg) led to a decrease in GABA hippocampal concentration. Altogether, the presented study provides a new insight into the involvement of the GABA-ergic system in the rewarding effects of mephedrone, implying that those effects are at least partially mediated through GABAB receptors, which suggests their potential role as new targets for the pharmacological management of mephedrone use disorder.
A Novel Bioactive Peptide, T14, Selectively Activates mTORC1 Signalling: Therapeutic Implications for Neurodegeneration and Other Rapamycin-Sensitive Applications
Authors: Ranglani Sanskar , Ashton Anna , Mahfooz Kashif , Komorowska Joanna , Graur Alexandru , Kabbani Nadine , Garcia-Rates Sara , Greenfield Susan
Published: June 2023

T14 modulates calcium influx via the α-7 nicotinic acetylcholine receptor to regulate cell growth. Inappropriate triggering of this process has been implicated in Alzheimer’s disease (AD) and cancer, whereas T14 blockade has proven therapeutic potential in in vitro, ex vivo and in vivo models of these pathologies. Mammalian target of rapamycin complex 1 (mTORC1) is critical for growth, however its hyperactivation is implicated in AD and cancer. T14 is a product of the longer 30mer-T30. Recent work shows that T30 drives neurite growth in the human SH-SY5Y cell line via the mTOR pathway. Here, we demonstrate that T30 induces an increase in mTORC1 in PC12 cells, and ex vivo rat brain slices containing substantia nigra, but not mTORC2. The increase in mTORC1 by T30 in PC12 cells is attenuated by its blocker, NBP14. Moreover, in post-mortem human midbrain, T14 levels correlate significantly with mTORC1. Silencing mTORC1 reverses the effects of T30 on PC12 cells measured via AChE release in undifferentiated PC12 cells, whilst silencing mTORC2 does not. This suggests that T14 acts selectively via mTORC1. T14 blockade offers a preferable alternative to currently available blockers of mTOR as it would enable selective blockade of mTORC1, thereby reducing side effects associated with generalised mTOR blockade.
Close Relationship between Systemic Arterial and Portal Venous Pressure in an Animal Model with Healthy Liver
Authors: Lazaro Adhara , Stoll Patrick , von Elverfeldt Dominik , Kreisel Wolfgang , Deibert Peter
Published: June 2023

It is unclear to what extent systemic arterial blood pressure influences portal pressure. This relationship is clinically important as drugs, which are conventionally used for therapy of portal hypertension, may also influence systemic arterial blood pressure. This study investigated the potential correlation between mean arterial (MAP) and portal venous pressure (PVP) in rats with healthy livers. In a rat model with healthy livers, we investigated the effect of manipulation of MAP on PVP. Interventions consisted of 0.9% NaCl (group 1), 0.1 mg/kg body weight (bw) Sildenafil (low dose), an inhibitor of phosphodiesterase-5 (group 2), and 1.0 mg/kg bw Sildenafil (high dose, group 3) in 600 µL saline injected intravenously. Norepinephrine was used to increase MAP in animals with circulatory failure while PVP was monitored. Injection of the fluids induced a transient drop in MAP and PVP, probably due to a reversible cardiac decompensation. The drop in MAP and drop in PVP are significantly correlated. The time lag between change in MAP and change in PVP by 24 s in all groups suggests a cause-and-effect relationship. Ten minutes after the injection of the fluid, cardiac function was normalized. Thereafter, MAP gradually decreased. In the NaCl group, PVP decreases by 0.485% for a 1% drop of MAP, by 0.550% in the low-dose sildenafil group, and by 0.651% in the high-dose sildenafil group (p < 0.05 for difference group two vs. group one, group three vs. group one, and group three vs. group two). These data suggest that Sildenafil has an inherent effect on portal pressure that exceeds the effect of MAP. Injection of norepinephrine led to a sudden increase in MAP followed by an increase in PVP after a time lag. These data show a close relationship between portal venous pressure and systemic arterial pressure in this animal model with healthy livers. A change in MAP is consequently followed by a change in PVP after a distinct time lag. This study, furthermore, suggests that Sildenafil influences portal pressure. Further studies should be performed in a model with cirrhotic livers, as these may be important in the evaluation of vasoactive drugs (e.g., PDE-5-inhibitors) for therapy of portal hypertension.
The Pannexin 1 Channel and the P2X7 Receptor Are in Complex Interplay to Regulate the Release of Soluble Ectonucleotidases in the Murine Bladder Lamina Propria
Authors: Aresta Branco Mafalda S. L. , Gutierrez Cruz Alejandro , Peri Lauren E. , Mutafova-Yambolieva Violeta N.
Published: June 2023

The bladder urothelium releases ATP into the lamina propria (LP) during filling, which can activate P2X receptors on afferent neurons and trigger the micturition reflex. Effective ATP concentrations are largely dependent on metabolism by membrane-bound and soluble ectonucleotidases (s-ENTDs), and the latter are released in the LP in a mechanosensitive manner. Pannexin 1 (PANX1) channel and P2X7 receptor (P2X7R) participate in urothelial ATP release and are physically and functionally coupled, hence we investigated whether they modulate s-ENTDs release. Using ultrasensitive HPLC-FLD, we evaluated the degradation of 1,N6-etheno-ATP (eATP, substrate) to eADP, eAMP, and e-adenosine (e-ADO) in extraluminal solutions that were in contact with the LP of mouse detrusor-free bladders during filling prior to substrate addition, as an indirect measure of s-ENDTS release. Deletion of Panx1 increased the distention-induced, but not the spontaneous, release of s-ENTDs, whereas activation of P2X7R by BzATP or high concentration of ATP in WT bladders increased both. In Panx1−/− bladders or WT bladders treated with the PANX1 inhibitory peptide 10Panx, however, BzATP had no effect on s-ENTDS release, suggesting that P2X7R activity depends on PANX1 channel opening. We concluded, therefore, that P2X7R and PANX1 are in complex interaction to regulate s-ENTDs release and maintain suitable ATP concentrations in the LP. Thus, while stretch-activated PANX1 hinders s-ENTDS release possibly to preserve effective ATP concentration at the end of bladder filling, P2X7R activation, presumably in cystitis, would facilitate s-ENTDs-mediated ATP degradation to counteract excessive bladder excitability.
Lysophosphatidic Acid Induces Podocyte Pyroptosis in Diabetic Nephropathy by an Increase of Egr1 Expression via Downregulation of EzH2
Authors: Kim Donghee , Ban Ka-Yun , Lee Geon-Ho , Jun Hee-Sook
Published: June 2023

Podocyte damage and renal inflammation are the main features and pathogenesis of diabetic nephropathy (DN). Inhibition of lysophosphatidic acid (LPA) receptor 1 (LPAR1) suppresses glomerular inflammation and improves DN. Herein, we investigated LPA-induced podocyte damage and its underlying mechanisms in DN. We investigated the effects of AM095, a specific LPAR1 inhibitor, on podocytes from streptozotocin (STZ)-induced diabetic mice. E11 cells were treated with LPA in the presence or absence of AM095, and the expression of NLRP3 inflammasome factors and pyroptosis were measured. A chromatin immunoprecipitation assay and Western blotting were performed to elucidate underlying molecular mechanisms. Gene knockdown by transfecting small interfering RNA was used to determine the role of the transcription factor Egr1 (early growth response protein 1) and histone methyltransferase EzH2 (Enhancer of Zeste Homolog 2) in LPA-induced podocyte injury. AM095 administration inhibited podocyte loss, NLRP3 inflammasome factor expression, and cell death in STZ-induced diabetic mice. In E11 cells, LPA increased NLRP3 inflammasome activation and pyroptosis via LPAR1. Egr1 mediated NLRP3 inflammasome activation and pyroptosis in LPA-treated E11 cells. LPA decreased H3K27me3 enrichment at the Egr1 promoter in E11 cells by downregulating EzH2 expression. EzH2 knockdown further increased LPA-induced Egr1 expression. In podocytes from STZ-induced diabetic mice, AM095 suppressed Egr1 expression increase and EzH2/H3K27me3 expression reduction. Collectively, these results demonstrate that LPA induces NLRP3 inflammasome activation by downregulating EzH2/H3K27me3 and upregulating Egr1 expression, resulting in podocyte damage and pyroptosis, which may be a potential mechanism of DN progression.
HDAC6 Deficiency Has Moderate Effects on Behaviors and Parkinson’s Disease Pathology in Mice
Authors: Zhao Jiayin , He Yongtao , Duan Yufei , Ma Yuanyuan , Dong Hongtian , Zhang Xiaoshuang , Fang Rong , Zhang Yunhe , Yu Mei , Huang Fang
Published: June 2023

Histone deacetylase 6 (HDAC6) is involved in the regulation of protein aggregation and neuroinflammation, but its role in Parkinson’s disease (PD) remains controversial. In this study, Hdac6−/− mice were generated by CRISPR-Cas9 technology for exploring the effect of HDAC6 on the pathological progression of PD. We found that male Hdac6−/− mice exhibit hyperactivity and certain anxiety. In the acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice, though motor injury was slightly alleviated by HDAC6 deficiency, dopamine (DA) depletion in the striatum, the decrease in the number of DA neurons in the substantia nigra (SN) and the reduction in DA neuronal terminals were not affected. In addition, activation of glial cells and the expression of α-synuclein, as well as the levels of apoptosis-related proteins in the nigrostriatal pathway, were not changed in MPTP-injected wild-type and Hdac6−/− mice. Therefore, HDAC6 deficiency leads to moderate alterations of behaviors and Parkinson’s disease pathology in mice.
Copper-Based Antibiotic Strategies: Exploring Applications in the Hospital Setting and the Targeting of Cu Regulatory Pathways and Current Drug Design Trends
Authors: Orta-Rivera Aixa M. , Meléndez-Contés Yazmary , Medina-Berríos Nataniel , Gómez-Cardona Adriana M. , Ramos-Rodríguez Andrés , Cruz-Santiago Claudia , González-Dumeng Christian , López Janangelis , Escribano Jansteven , Rivera-Otero Jared J. , Díaz-Rivera Josean , Díaz-Vélez Sebastián C. , Feliciano-Delgado Zulemaría , Tinoco Arthur D.
Published: June 2023

Classical antibacterial drugs were designed to target specific bacterial properties distinct from host human cells to maximize potency and selectivity. These designs were quite effective as they could be easily derivatized to bear next-generation drugs. However, the rapid mutation of bacteria and their associated acquired drug resistance have led to the rise of highly pathogenic superbug bacterial strains for which treatment with first line drugs is no match. More than ever, there is a dire need for antibacterial drug design that goes beyond conventional standards. Taking inspiration by the body’s innate immune response to employ its own supply of labile copper ions in a toxic attack against pathogenic bacteria, which have a very low Cu tolerance, this review article examines the feasibility of Cu-centric strategies for antibacterial preventative and therapeutic applications. Promising results are shown for the use of Cu-containing materials in the hospital setting to minimize patient bacterial infections. Studies directed at disrupting bacterial Cu regulatory pathways elucidate new drug targets that can enable toxic increase of Cu levels and perturb bacterial dependence on iron. Likewise, Cu intracellular chelation/prochelation strategies effectively induce bacterial Cu toxicity. Cu-based small molecules and nanoparticles demonstrate the importance of the Cu ions in their mechanism and display potential synergism with classical drugs.
Supramolecular Structure and Antimicrobial Activity of Ni(II) Complexes with s-Triazine/Hydrazine Type Ligand
Authors: Fathalla Eman M. , Abu-Youssef Morsy A. M. , Sharaf Mona M. , El-Faham Ayman , Barakat Assem , Haukka Matti , Soliman Saied M.
Published: June 2023

The two complexes, [Ni(DPPT)2](NO3)2*1.5H2O (1) and [Ni(DPPT)(NO3)Cl].EtOH (2), were synthesized using the self-assembly of (E)-2,4-di(piperidin-1-yl)-6-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)-1,3,5-triazine (DPPT) with Ni(NO3)2*6H2O in the absence and presence of NiCl2*6H2O, respectively. In both cases, the neutral tridentate DPPT ligand is found coordinated to the Ni(II) via three N-atoms from the hydrazone, pyridine and s-triazine rings. Hence, the homoleptic complex 1 has a NiN6 hexa-coordination environment while two NO3− are counter anions in addition to one-and-a-half crystallized hydration water molecules are found acting as an outer sphere. The heteroleptic complex 2 has a NiN3O2Cl coordination sphere where the coordination environment of the Ni(II) is completed by one bidentate nitrate and one chloride ion leading to a neutral inner sphere while the outer sphere contains one crystallized ethanol molecule. Both complexes have distorted octahedral coordination environments around the Ni(II) ion. Using Hirshfeld analysis, the intermolecular contacts H…H and O…H in 1 and the Cl…H, O…H, N…H, H…H, C…H and C…C in 2 are found to be the most important for crystal stability. The antimicrobial activity of complexes 1 and 2 was assessed against different bacterial and fungal strains, and the results were compared with the free ligand as well as the antibacterial (Gentamycin) and antifungal (Ketoconazole) positive controls. Both Ni(II) complexes are better antibacterial and antifungal agents than the free ligand. Interestingly, both Ni(II) complexes have similar antifungal activity against C. albicans compared to Ketoconazole.
Frequency and Clinical Impact of Family History of Coronary Artery Disease in Patients with Vasospastic Angina
Authors: Teragawa Hiroki , Uchimura Yuko , Oshita Chikage , Hashimoto Yu , Nomura Shuichi
Published: June 2023

Background: Family history (FH) of coronary artery disease (CAD) [FH-CAD] is a well-known risk factor for atherosclerotic CAD. However, FH-CAD frequency in patients with vasospastic angina (VSA) remains unknown, and the clinical characteristics and prognosis of VSA patients with FH-CAD are unclear. Therefore, this study compared FH-CAD frequency between patients with atherosclerotic CAD and those with VSA and examined the clinical characteristics and prognosis of VSA patients with FH-CAD. Methods: Coronary angiography and spasm provocation tests (SPT) were used to investigate chest pain of coronary artery origin in patients classified into atherosclerotic CAD (362 cases), VSA (221 cases; positive for SPT) and non-VSA (73 cases; negative for SPT) groups, with FH-CAD being defined. In the VSA group, flow-mediated vasodilation (FMD) and nitroglycerin-independent vasodilation (NID) via brachial artery echocardiography and clinical symptoms in the groups with and without FH-CAD were checked, with Kaplan–Meier curves revealing major adverse cardiovascular events (cardiac death and rehospitalisation for cardiovascular disease) between the two groups. Results: The atherosclerotic CAD group had a significantly lower FH-CAD frequency (12%, p = 0.029) than the VSA (19%) and non-VSA groups (19%). FH-CAD was more common in females in the VSA and non-VSA groups than in the atherosclerotic CAD group (p < 0.001). Nonpharmacological treatment for CAD in FH-CAD was more common in the atherosclerotic CAD group (p = 0.017). In the VSA group, FH-CAD tended to be more common in females (p = 0.052). Although no differences in FMD of the brachial artery were observed between the groups, the FH-CAD (+) group had significantly higher NID than the FH-CAD (−) group (p = 0.023). Kaplan–Meier’s analysis revealed a similar prognosis between the two groups, and other clinical characteristics did not differ. Conclusion: Patients with VSA have a higher FH-CAD frequency than those with atherosclerotic CAD, especially in females. Although FH-CAD may affect vascular function in patients with VSA, its effect on the severity and prognosis of VSA appears to be minimal. FH-CAD and its confirmation may assist in CAD diagnosis, especially in female patients.
Optimal Design and Performance Analysis of a Hybrid System Combining a Semi-Submersible Wind Platform and Point Absorbers
Authors: Zhou Binzhen , Hu Jianjian , Zhang Qi , Wang Lei , Jing Fengmei , Collu Maurizio
Published: June 2023

Integrating point absorber wave energy converters (PAWECs) and an offshore floating wind platform provide a cost-effective way of joint wind and wave energy exploitation. However, the coupled dynamics of the complicated hybrid system and its influence on power performance are not well understood. Here, a frequency-domain-coupled hydrodynamics, considering the constraints and the power output through the relative motion between the PAWECs and the semi-submersible platform, is introduced to optimize the size, power take-off damping, and layout of the PAWECs. Results show that the annual wave power generation of a PAWEC can be improved by 30% using a 90° conical or a hemispherical bottom instead of a flat bottom. Additionally, while letting the PAWECs protrude out the sides of the triangular frame of the platform by a distance of 1.5 times the PAWEC radius, the total power generation can be improved by up to 18.2% without increasing the motion response of the platform. The PAWECs can reduce the resonant heave motion of the platform due to the power take-off damping force. This study provides a reference for the synergistic use of wave and wind energy.
Methodological Design Optimization of a Marine LNG Internal Combustion Gas Engine to Burn Alternative Fuels
Authors: Ruiz Zardoya Ander , Oregui Bengoetxea Iñigo , Lopez Martinez Angel , Loroño Lucena Iñaki , Orosa José A.
Published: June 2023

Marine emission policies are becoming more demanding; thus, ship propulsion and power generation technologies need to be adapted to current scenarios. LNG is already considered to be a transition fuel, and new alternative marine fuels are emerging. The aim of this study was to develop an innovative methodology to optimize and adapt the combustion system of an LNG internal combustion marine engine to burn alternative marine fuels. The present study was based on LBG, but the methodology could be replicated with other fuels. A total of six tests were carried out, with three prechamber designs and three spark plug designs. Each test was carried out in a single-cylinder engine with two types of high-methane-number fuel. The influence on thermal efficiency parameters such as the prechamber volume, the orientation of the flame holes, and the existence of a central hole was studied. In the case of the spark plug, the influence of the amount of precious metal in the electrode, its shape and its insertion into the prechamber were analysed. Experiments showed that by modifying both the prechamber and the spark plug, maximum improvements in thermal efficiency of 1.9% can be achieved. Those improvements allowed the LBG engine to suffer only a 4.3% thermal efficiency reduction, as opposed to its LNG counterpart. By applying the proposed methodology, the thermal efficiency of commercially available internal combustion gas engines could be improved.
Phytoplankton Dynamics and Biogeochemistry of the Black Sea
Authors: Silkin Vladimir , Pautova Larisa , Podymov Oleg , Chasovnikov Valeryi , Lifanchuk Anna , Fedorov Alexey , Kluchantseva Agnislava
Published: June 2023

The biogeochemistry of waters is an essential regulator of phytoplankton dynamics, determining the level of species bloom and the change in dominants. This paper investigated the seasonal dynamics of phytoplankton and the nutrient concentrations and their ratios in the northeastern Black Sea in 2017–2021. Two taxonomic groups, diatoms and coccolithophores, determine the seasonal dynamics and significantly contribute to the total phytoplankton biomass. Coccolithophores formed blooms in early June annually, except in 2020. Large diatoms dominated in summer with a biomass exceeding 1000 mg m−3 annually, except in 2019. During the blooms of these taxonomic groups, their contribution to the total phytoplankton biomass exceeded 90%. Each group has characteristic biogeochemical niches in the nitrogen and phosphorus concentration coordinates. The position of the seasonal thermocline regulates the biogeochemistry of the water. With a high-lying and sharp gradient thermocline (the average for five years is 6.87 m), low nitrogen concentrations and a nitrogen-to-phosphorus ratio below the Redfield ratio are created in the upper mixed layer. These conditions are optimal for the dominance of coccolithophores. When the thermocline is deepened (the average for five years is 17.96 m), the phosphorus concentration decreases significantly and the ratio of nitrogen to phosphorus is significantly higher than the Redfield ratio, and these conditions lead to the dominance of large diatoms. The results of experimental studies with nitrogen and phosphorus additives in the natural phytoplankton population confirm the above statements. The addition of phosphorus leads to the increased role of coccolithophores in the total phytoplankton biomass, the addition of nitrogen alone contributes to the growth of large diatoms, and the combined addition of phosphorus and nitrogen in a ratio close to the Redfield ratio leads to the dominance of small diatoms.
Genetic Diversity of Lecanosticta acicola in Pinus Ecosystems in Northern Spain
Authors: Mesanza Nebai , Barnes Irene , van der Nest Ariska , Raposo Rosa , Berbegal Mónica , Iturritxa Eugenia
Published: June 2023

Lecanosticta acicola is one of the most damaging species affecting Pinus radiata plantations in Spain. Favourable climatic conditions and unknown endogenous factors of the pathogen and host led to a situation of high incidence and severity of the disease in these ecosystems. With the main aim of understanding the factors intrinsic to this pathogenic species, a study of the population structure in new established plantations with respect to older plantations was implemented. The genetic diversity, population structure and the ability of the pathogen to spread was determined in Northern Spain (Basque Country), where two thirds of the total Pinus radiata plantations of Spain are located. From a total of 153 Lecanosticta acicola isolates analysed, two lineages were present; the southern lineage, which was prevalent, and the northern lineage, which was scarce. A total of 22 multilocus genotypes were detected with a balanced composition of both mating types and evidence for sexual reproduction. In addition to the changing environmental conditions enhancing disease expression, the complexity and diversity of the pathogen will make it difficult to control and to maintain the wood productive system fundamentally based on this forest species.