bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptation of High Spatio-Temporal Resolution Weather/Load Forecast in Real-World Distributed Energy-System Operation
Authors: Safaei Pirooz Amir Ali , Sanjari Mohammad J. , Kim Young-Jin , Moore Stuart , Turner Richard , Weaver Wayne W. , Srinivasan Dipti , Guerrero Josep M. , Shahidehpour Mohammad
Published: April 2023

Despite significant advances in distributed renewable energy systems (DRES), the technology still faces several substantial challenges that prevent the large-scale adoption of these systems into a country’s energy sector. The intermittency of renewables, uncertainties associated with real-time multi-horizon weather and load forecasts, and lack of comprehensive control systems are among the main technical and regulatory challenges for the real-world adoption of DRES. This paper outlines the current state of knowledge in the real-world operation of DRES and also describes pathways and methodologies that enable and facilitate the uptake of DRES in a country’s energy sector.
A Review of Mineral and Rock Wettability Changes Induced by Reaction: Implications for CO2 Storage in Saline Reservoirs
Authors: Chen Ting , Song Laiming , Zhang Xueying , Yang Yawen , Fan Huifang , Pan Bin
Published: April 2023

Wettability in CO2-brine-mineral/rock systems is an important parameter influencing CO2 storage capacities and leakage risks in saline reservoirs. However, CO2 tends to react with various minerals and rocks at subsurface conditions, thus causing temporal and spatial wettability changes. Although many relevant research works have been published during past years, a thorough overview of this area is still lacking. Therefore herein, reaction-induced wettability changes are reviewed, and the underlying mechanisms are discussed. Current research gaps are identified, future outlooks are suggested, and some conclusions are drawn. The fundamental understanding of reaction-induced mineral and rock wettability changes during CO2 storage in saline reservoirs is analyzed and the guidance for long-term CO2 containment security evaluations is provided.
Research on Online Detection Method of Transformer Winding Deformation Based on VFTO Characteristics
Authors: Shi Xinghua , Wei Ran , Zhang Wenbin
Published: April 2023

At present, most of the winding fault detections of transformers use offline methods, which require the entire line to be powered off or after the transformer has been shut down due to a serious fault, and they cannot detect the running status of the windings in real time and online. Since the transformer will be impacted by VFTO during operation, the VFTO is used as the excitation, and the basic principle of the frequency response method is used to propose an online detection method of transformer winding deformation based on VFTO characteristics. The finite element software is used to calculate the equivalent circuit parameters of normal and deformed windings, and the equivalent circuit model of the transformer windings before and after deformation is established. Due to the uncertainty of the VFTO waveform, combined with the frequency response method, the VFTO waveform is injected into the transformer winding health, and the frequency response curve is obtained from the deformed equivalent circuit, which is used to analyze the change of the resonance point in the case of radial deformation, axial deformation, and axial displacement of the winding. The simulation results show that with VFTO as the excitation, the obtained resonance point change can comprehensively reflect the deformation information of the winding. At the same time, the feasibility of the method is verified by experiments.
Full-Length Transcriptome Analysis of the Secondary-Growth-Related Genes of Pinus massoniana Lamb. with Different Diameter Growth Rates
Authors: Zhou Zijing , Ding Guijie , Li Zhengchun , Fan Fuhua
Published: April 2023

Secondary growth is the main source of wood accumulation and has an extremely complex regulation process. Pinus massoniana Lamb. is one of the main timber tree species in China and it is of great significance in the study of the secondary growth process. The full-length transcriptome from the stems of P. massoniana with different diameter growth rates was obtained by PacBio and 15,448 full-length transcripts were identified. A comparative transcriptome analysis revealed that 408 genes were differentially expressed between the fast-growing wood (FGW) and slow-growing wood (SGW). The important regulatory genes involved in the secondary growth of P. massoniana (cell division, cell wall biosynthesis, lignification, and programmed cell death), such as ARL8, POD, EXPA8, Ecm33, and RhoA, were identified by a GO and KEGG annotation analysis. The differential expression of the key genes in the lignin synthesis pathway were obtained, such as PAL, 4CL, CCR, HCT, and PER. In addition, the abscisic acid receptor gene PYL and the ethylene biosynthesis key gene EFE were screened for their involvement in the regulation of the secondary growth of P. massoniana. It is speculated that these genes coordinate the processes of secondary growth to promote the rapid growth of FGW. This study preliminarily explored the differential mechanism of the growth rate of P. massoniana and provided a reference for obtaining new P. massoniana germplasm with a high quality and excellent yield.
Temporal Variation in Von Bertalanffy Growth Curves and Generation Time of Southern Gulf of St. Lawrence Spring and Fall Spawning Atlantic Herring (Clupea harengus)
Authors: Burbank Jacob , McDermid Jenni L. , Turcotte François , Rolland Nicolas
Published: April 2023

Examining temporal changes in the growth and generation time of fish species can be valuable for understanding population responses to different management measures and environmental conditions. Atlantic herring (Clupea harengus-Linnaeus, 1758) is an ecologically and commercially important pelagic forage fish species that occupies the southern Gulf of St. Lawrence. Here, we developed von Bertalanffy growth curves and estimated yearly values of generation time for NAFO Division 4TVn Atlantic herring for the years from 1988 to 2021. The results indicate a temporal reduction in the growth and generation time of both spring and fall spawning herring. Over the time series, the generation time of spring and fall spawners reduced by approximately 1 and 2 years, respectively. Furthermore, the average generation time of spring spawners across the time series (6.23 years (95% CI: 5.78–6.85 years)) was approximately 1 year lower than that of fall spawners (7.52 years (6.82–8.34 years)). Overall, the findings of this study can be used to better inform stock assessments and rebuilding plans for 4TVn spring and fall spawning Atlantic herring and highlight the importance of examining temporal trends in growth and generation time for more effective management of fish stocks.
Comparative Responses of Silicon to Reduce Cadmium and Enrich Selenium in Rice Varieties
Authors: Su Yang , Huang Xin , Li Ling , Muhammad Zahir Ahsan , Li Meilin , Zheng Tengda , Guo Zhe , Zhang Yue , Luo Dan , Ye Xiaoying , Jia Xiaomei , Hussain Panhwar Faiz , Tun Myo Thuzar , Zhu Jianqing
Published: April 2023

Cadmium (Cd), a highly toxic heavy metal for crops in China, poses a significant threat to rice cultivation. It is crucial to identify the genotypes with robust resistance to heavy metals, including Cd, in rice. The experiment was conducted to examine the mitigation effect of silicon (Si) on Cd toxicity levels in Se-enriched Z3055B and non-Se-enriched G46B rice genotypes. A basal dose of Si improved the growth and the quality of rice significantly by reducing the Cd content in rice roots, stems, leaves and grains and increased the yield, biomass and selenium (Se) content of brown rice in both genotypes. Additionally, Se content in brown rice and polished rice was notably higher in Se-enriched rice than in non-Se-enriched rice, with the highest amount at 0.129 mg/kg and 0.085 mg/kg, respectively. The results demonstrated that a basal fertilizer concentration of 30 mg/kg of Si was more effective in reducing Cd transport from roots to shoots in Se-enriched rice than in non-Se-enriched rice genotypes. Therefore, it can be concluded that Se-enriched rice genotypes are a viable option for food crop production in Cd-contaminated areas.
Co-Extraction Technique Improves Functional Capacity and Health-Related Benefits of Olive Oils: A Mini Review
Authors: Marx Ítala M. G.
Published: April 2023

Olive oil, a fundamental component of the Mediterranean diet, is recognized as a functional food due to its health-promoting composition. The concentration of phenolic compounds in olive oil is influenced by various factors such as genetics, agro-climatic conditions, and technological processes. Therefore, to ensure an ideal intake of phenolics through the diet, it is recommended to produce functional enriched olive oil that contains a high concentration of bioactive compounds. The co-extraction technique is used to create innovative and differentiated products that promote the sensory and health-related composition of oils. To enrich olive oil, various natural sources of bioactive compounds can be used, including raw materials derived from the same olive tree such as olive leaves, as well as other compounds from plants and vegetables, such as herbs and spices (garlic, lemon, hot pepper, rosemary, thyme, and oregano). The development of functional enriched olive oils can contribute to the prevention of chronic diseases and improve consumers’ quality of life. This mini-review compiles and discusses relevant scientific information related to the development of enriched olive oil using the co-extraction technique and its positive effects on the health-related composition of oils.
Saccharina japonica Ethanol Extract Ameliorates Dextran Sulfate Sodium-Induced Colitis via Reshaping Intestinal Microenvironment and Alleviating Inflammatory Response
Authors: Lu Kuan , Liu Lin , Lin Pengcheng , Dong Xiufang , Ni Laixue , Che Hongxia , Xie Wancui
Published: April 2023

Saccharina japonica belongs to brown macro-alga with various potential health benefits; its antioxidant and anti-inflammatory activities indicate the potential to improve inflammatory bowel diseases. Here, the potential anti-colitis effect of Saccharina japonica extract (SJE) was evaluated on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in C57B/L6 mice. The mice were treated with mesalazine (MES) and various doses of SJE by gavage for 14 days. Results showed that both MES and SJE treatment decreased the disease activity index scores, relieving the short colon. SJE increased the occludin and zonula occludens-1 levels, and the beneficial effects were better than MES. MES and SJE exerted similar effects in decreasing inflammatory cytokines and oxidative stress. Moreover, SJE reshaped the intestinal microbiota by increasing α-diversity and reducing plenty of harmful bacteria. Dietary SJE was significant to relieving the reduction in short-chain fatty acids. The results revealed the protective effect of SJE on colitis and potential mechanisms, which is important for the rational use of SJE in UC prevention.
Fractional Itô–Doob Stochastic Differential Equations Driven by Countably Many Brownian Motions
Authors: Ben Makhlouf Abdellatif , Mchiri Lassaad , Othman Hakeem A. , Rguigui Hafedh M. S.
Published: April 2023

This article is devoted to showing the existence and uniqueness (EU) of a solution with non-Lipschitz coefficients (NLC) of fractional Itô-Doob stochastic differential equations driven by countably many Brownian motions (FIDSDECBMs) of order ϰ∈(0,1) by using the Picard iteration technique (PIT) and the semimartingale local time (SLT).
Fast and Accurate Numerical Algorithm with Performance Assessment for Nonlinear Functional Volterra Equations
Authors: Nwaigwe Chinedu , Micula Sanda
Published: April 2023

An efficient numerical algorithm is developed for solving nonlinear functional Volterra integral equations. The core idea is to define an appropriate operator, then combine the Krasnoselskij iterative scheme with collocation at discrete points and the Newton–Cotes quadrature rule. This results in an explicit scheme that does not require solving a nonlinear or linear algebraic system. For the convergence analysis, the discretization error is estimated and proved to converge via a recurrence relation. The discretization error is combined with the Krasnoselskij iteration error to estimate the total approximation error, hence establishing the convergence of the method. Then, numerical experiments are provided, first, to demonstrate the second order convergence of the proposed method, and secondly, to show the better performance of the scheme over the existing nonlinear-based approach.
Family History Research and Distressing Emotions
Authors: Moore Susan M.
Published: April 2023

Anecdotal evidence suggests that the popular pastime of exploring one’s family history can unleash strong emotions, both positive and negative. The aim of this study was to chart the extent and nature of negative emotions among family historians, and profile those most vulnerable to distress. Data from an online survey of 775 adult Australian hobbyist family historians showed nearly two-thirds experienced strong distressing emotions such as anger, shock and sadness while researching their forebears. Triggers included discoveries which led to feelings of betrayal and distrust or posed moral dilemmas. Also distressing were findings about ancestors who behaved badly, were treated cruelly/unfairly, or who experienced tragedy. Family historians who reported strong negative emotions were more likely than those who did not to be younger, female, spend more time on their hobby, have half-siblings, driven by the motive for greater self-understanding, and score higher on the personality trait of openness to experience but lower on emotional stability. The study is important because it raises issues of (a) what support is available to family historians who find their discoveries strongly distressing and (b) whether purveyors of genealogical research products should provide more education and support to their clients.
Interaction between KLOTHO-VS Heterozygosity and APOE ε4 Allele Predicts Rate of Cognitive Decline in Late-Onset Alzheimer’s Disease
Authors: Chen Xi Richard , Shao Yongzhao , Sadowski Martin J. ,   on behalf of the Alzheimer’s Disease Neuroimaging Initiative
Published: April 2023

KLOTHO-VS heterozygosity (KL-VShet+) promotes longevity and protects against cognitive decline in aging. To determine whether KL-VShet+ mitigates Alzheimer’s disease (AD) progression, we used longitudinal linear-mixed models to compare the rate of change in multiple cognitive measures in AD patients stratified by APOE ε4 carrier status. We aggregated data on 665 participants (208 KL-VShet−/ε4−, 307 KL-VShet−/ε4+, 66 KL-VShet+/ε4−, and 84 KL-VShet+/ε4+) from two prospective cohorts, the National Alzheimer’s Coordinating Center and the Alzheimer’s Disease Neuroimaging Initiative. All participants were initially diagnosed with mild cognitive impairment, later developed AD dementia during the study, and had at least three subsequent visits. KL-VShet+ conferred slower cognitive decline in ε4 non-carriers (+0.287 MMSE points/year, p = 0.001; −0.104 CDR-SB points/year, p = 0.026; −0.042 ADCOMS points/year, p < 0.001) but not in ε4 carriers who generally had faster rates of decline than non-carriers. Stratified analyses showed that the protective effect of KL-VShet+ was particularly prominent in male participants, those who were older than the median baseline age of 76 years, or those who had an education level of at least 16 years. For the first time, our study provides evidence that KL-VShet+ status has a protective effect on AD progression and interacts with the ε4 allele.
Detection of a Novel MSI2-C17orf64 Transcript in a Patient with Aggressive Adenocarcinoma of the Gastroesophageal Junction: A Case Report
Authors: Ferrari Anna , Fiocca Roberto , Bonora Elena , Domizio Chiara , Fonzi Eugenio , Angeli Davide , Domenico Raulli Gian , Mattioli Sandro , Martinelli Giovanni , Molinari Chiara
Published: April 2023

Adenocarcinoma of the esophagus (EAC) and gastroesophageal junction (GEJ-AC) is associated with poor prognosis, treatment resistance and limited systemic therapeutic options. To deeply understand the genomic landscape of this cancer type, and potentially identify a therapeutic target in a neoadjuvant chemotherapy non-responder 48-year-old man, we adopted a multi-omic approach. We simultaneously evaluated gene rearrangements, mutations, copy number status, microsatellite instability and tumor mutation burden. The patient displayed pathogenic mutations of the TP53 and ATM genes and variants of uncertain significance of three kinases genes (ERBB3, CSNK1A1 and RPS6KB2), along with FGFR2 and KRAS high copy number amplification. Interestingly, transcriptomic analysis revealed the Musashi-2 (MSI2)-C17orf64 fusion that has never been reported before. Rearrangements of the RNA-binding protein MSI2 with a number of partner genes have been described across solid and hematological tumors. MSI2 regulates several biological processes involved in cancer initiation, development and resistance to treatment, and deserves further investigation as a potential therapeutic target. In conclusion, our extensive genomic characterization of a gastroesophageal tumor refractory to all therapeutic approaches led to the discovery of the MSI2-C17orf64 fusion. The results underlie the importance of deep molecular analyses enabling the identification of novel patient-specific markers to be monitored during therapy or even targeted at disease evolution.
The Potential Regulation of A-to-I RNA Editing on Genes in Parkinson’s Disease
Authors: Wu Sijia , Xue Qiuping , Qin Xinyu , Wu Xiaoming , Kim Pora , Chyr Jacqueline , Zhou Xiaobo , Huang Liyu
Published: April 2023

Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration and an abnormal accumulation of α-synuclein aggregates. A number of genetic factors have been shown to increase the risk of PD. Exploring the underlying molecular mechanisms that mediate PD’s transcriptomic diversity can help us understand neurodegenerative pathogenesis. In this study, we identified 9897 A-to-I RNA editing events associated with 6286 genes across 372 PD patients. Of them, 72 RNA editing events altered miRNA binding sites and this may directly affect miRNA regulations of their host genes. However, RNA editing effects on the miRNA regulation of genes are more complex. They can (1) abolish existing miRNA binding sites, which allows miRNAs to regulate other genes; (2) create new miRNA binding sites that may sequester miRNAs from regulating other genes; or (3) occur in the miRNA seed regions and change their targets. The first two processes are also referred to as miRNA competitive binding. In our study, we found 8 RNA editing events that may alter the expression of 1146 other genes via miRNA competition. We also found one RNA editing event that modified a miRNA seed region, which was predicted to disturb the regulation of four genes. Considering the PD-related functions of the affected genes, 25 A-to-I RNA editing biomarkers for PD are proposed, including the 3 editing events in the EIF2AK2, APOL6, and miR-4477b seed regions. These biomarkers may alter the miRNA regulation of 133 PD-related genes. All these analyses reveal the potential mechanisms and regulations of RNA editing in PD pathogenesis.
Identification of the Function of the Pathogenesis-Related Protein GmPR1L in the Resistance of Soybean to Cercospora sojina Hara
Authors: Du Yeyao , Amin Nooral , Ahmad Naveed , Zhang Hanzhu , Zhang Ye , Song Yang , Fan Sujie , Wang Piwu
Published: April 2023

Pathogenesis-related proteins, often used as molecular markers of disease resistance in plants, can enable plants to obtain systemic resistance. In this study, a gene encoding a pathogenesis-related protein was identified via RNA-seq sequencing analysis performed at different stages of soybean seedling development. Because the gene sequence showed the highest similarity with PR1L sequence in soybean, the gene was named GmPR1-9-like (GmPR1L). GmPR1L was either overexpressed or silenced in soybean seedlings through Agrobacterium-mediated transformation to examine the resistance of soybean to infection caused by Cercospora sojina Hara. The results revealed that GmPR1L-overexpressing soybean plants had a smaller lesion area and improved resistance to C. sojina infection, whereas GmPR1L-silenced plants had low resistance to C. sojina infection. Fluorescent real-time PCR indicated that overexpression of GmPR1L induced the expression of genes such as WRKY, PR9, and PR14, which are more likely to be co-expressed during C. sojina infection. Furthermore, the activities of SOD, POD, CAT, and PAL were significantly increased in GmPR1L-overexpressing soybean plants after seven days of infection. The resistance of the GmPR1L-overexpressing lines OEA1 and OEA2 to C. sojina infection was significantly increased from a neutral level in wild-type plants to a moderate level. These findings predominantly reveal the positive role of GmPR1L in inducing resistance to C. sojina infection in soybean, which may facilitate the production of improved disease-resistant soybean cultivars in the future.
Saudi Community-Based Screening Study on Genetic Variants in β-Cell Dysfunction and Its Role in Women with Gestational Diabetes Mellitus
Authors: Alshammary Amal F. , Al-Hakeem Malak Mohammed , Ali Khan Imran
Published: April 2023

Background: Diabetes (hyperglycemia) is defined as a multifactorial metabolic disorder in which insulin resistance and defects in pancreatic β-cell dysfunction are two major pathophysiologic abnormalities that underpin towards gestational diabetes mellitus (GDM). TCF7L2, KCNQ1, and KCNJ11 genes are connected to the mechanism of β-cell dysfunction. The purpose of this study was to investigate the genes associated with β-cell dysfunction and their genetic roles in the rs7903146, rs2237892, and rs5219 variants in Saudi women diagnosed with type 2 diabetes mellitus and GDM. Materials and Methods: In this case-control study, 100 women with GDM and 100 healthy volunteers (non-GDM) were recruited. Genotyping was performed using polymerase chain reaction (PCR), followed by restriction fragment length analysis. Validation was performed using Sanger sequencing. Statistical analyses were performed using multiple software packages. Results: Clinical studies showed a β-cell dysfunction positive association in women with GDM when compared to non-GDM women (p < 0.05). Both rs7903146 (CT vs. CC: OR-2.12 [95%CI: 1.13–3.96]; p = 0.01 & T vs. C: (OR-2.03 [95%CI: 1.32–3.11]; p = 0.001) and rs5219 SNPs (AG vs. AA: OR-3.37 [95%CI: 1.63–6.95]; p = 0.0006 & G vs. A: OR-3.03 [95%CI: 1.66–5.52]; p = 0.0001) showed a positive association with genotype and allele frequencies in women with GDM. ANOVA analysis confirmed that weight (p = 0.02), BMI (p = 0.01), and PPBG (p = 0.003) were associated with rs7903146 and BMI (p = 0.03) was associated with rs2237892 SNPs. Conclusions: This study confirms that the SNPs rs7903146 (TCF7L2) and rs5219 (KCNJ11) are strongly associated with GDM in the Saudi population. Future studies should address the limitations of this study.
Genome-Wide Identification, Characterization, and Expression of TCP Genes Family in Orchardgrass
Authors: Wang Cheng , Feng Guangyan , Xu Xiaoheng , Huang Linkai , Nie Gang , Li Dandan , Zhang Xinquan
Published: April 2023

Plant-specific TCP transcription factors regulate several plant growth and development processes. Nevertheless, little information is available about the TCP family in orchardgrass (Dactylis glomerata L.). This study identified 22 DgTCP transcription factors in orchardgrass and determined their structure, phylogeny, and expression in different tissues and developmental stages. The phylogenetic tree classified the DgTCP gene family into two main subfamilies, including class I and II supported by the exon–intron structure and conserved motifs. The DgTCP promoter regions contained various cis-elements associated with hormones, growth and development, and stress responses, including MBS (drought inducibility), circadian (circadian rhythms), and TCA-element (salicylic acid responsiveness). Moreover, DgTCP9 possibly regulates tillering and flowering time. Additionally, several stress treatments upregulated DgTCP1, DgTCP2, DgTCP6, DgTCP12, and DgTCP17, indicting their potential effects regarding regulating responses to the respective stress. This research offers a valuable basis for further studies of the TCP gene family in other Gramineae and reveals new ideas for increasing gene utilization.
Editorial for the Genetics of Muscular Dystrophies from the Pathogenesis to Gene Therapy Special Issue
Authors: Politano Luisa , Santorelli Filippo M.
Published: April 2023

Muscular dystrophies (MDs) make up a clinically and genetically heterogeneous group of skeletal muscle diseases with progressive muscle weakness and atrophy [...]
Sleep Quality between Nurses and the General Population during the COVID-19 Pandemic in Portugal: What Are the Differences?
Authors: Sampaio Francisco , Gaspar Susana , Fonseca César , Lopes Manuel José , Paiva Teresa , Guedes de Pinho Lara
Published: April 2023

Although several studies have described the impact of the COVID-19 pandemic, particularly on sleep quality, there are few studies that, in the same time period and using the same assessment tools, compare sleep quality and mental health status between nurses and the general population. Thus, the aim of this study was to (a) examine whether there were differences between nurses and the general population regarding sleep quality and mental health status during the COVID-19 pandemic and (b) identify which factors may explain sleep quality during the COVID-19 pandemic. To do that, we carried out a cross-sectional study in Portugal. Data were collected using an online survey platform during the first COVID-19 wave, from April to August 2020. Nurses presented poorer sleep quality than the general population, as well as higher anxiety levels. Irritability and worries about the future were two of the factors that might explain those differences. Thus, we can conclude that irritability and worries about the future are dimensions of anxiety that were associated with poor sleep quality during the COVID-19 pandemic. Thus, it would be important to adopt regular anxiety and sleep assessments, particularly for nurses, and to implement strategies to reduce this problem.
Is Gender an Antecedent to Workplace Stressors? A Systematic Review and an Empirical Study Using a Person-Centred Approach
Authors: Fida Roberta , Watson David , Ghezzi Valerio , Barbaranelli Claudio , Ronchetti Matteo , Di Tecco Cristina
Published: April 2023

Objective: Work is a key domain of life in which gender inequality can manifest, yet gender is rarely the explicit focus of research seeking to understand exposure to stressors. We investigated this research gap in two studies. Methods: Study 1 was a systematic review of the relationship between gender and key stressors (e.g., high demands, poor support, lack of clarity and control). From a total of 13,376,130 papers met our inclusion criteria. Study 2 was a cross-sectional study that included 11,289 employees nested within 71 public organisations (50.6% men). Through a latent profile analysis, we investigated the profiles of stressors separately from men and women. Results: The systematic review revealed that, for all stressors, a significant proportion of studies found no significant gender differences, and the review found mixed evidence of greater exposure for both men and women. The results of Study 2 revealed that both genders could be optimally represented by three psychosocial risk profiles reflecting medium, low and high stressors. The results also showed that while the shape of profiles was similar for both genders, men had a higher probability than women of being in the virtuous (i.e., low stressors) profile, and the opposite pattern emerged for the average profile (i.e., medium levels of stressors). Men and women displayed the same likelihood of being classified in the at-risk profile (i.e., high levels of stressors). Conclusion: Gender differences in exposure to stressors are inconsistent. Although the literature on gender role theory and the gendering of work suggests different exposures to stressors in men and women, we find little empirical support for this.
Altered Brain Expression of DNA Methylation and Hydroxymethylation Epigenetic Enzymes in a Rat Model of Neuropathic Pain
Authors: Rodrigues Diogo , Monteiro Clara , Cardoso-Cruz Helder , Galhardo Vasco
Published: April 2023

The role of epigenetics in chronic pain at the supraspinal level is yet to be fully characterized. DNA histone methylation is crucially regulated by de novo methyltransferases (DNMT1-3) and ten-eleven translocation dioxygenases (TET1-3). Evidence has shown that methylation markers are altered in different CNS regions related to nociception, namely the dorsal root ganglia, the spinal cord, and different brain areas. Decreased global methylation was found in the DRG, the prefrontal cortex, and the amygdala, which was associated with decreased DNMT1/3a expression. In contrast, increased methylation levels and mRNA levels of TET1 and TET3 were linked to augmented pain hypersensitivity and allodynia in inflammatory and neuropathic pain models. Since epigenetic mechanisms may be responsible for the regulation and coordination of various transcriptional modifications described in chronic pain states, with this study, we aimed to evaluate the functional role of TET1-3 and DNMT1/3a genes in neuropathic pain in several brain areas. In a spared nerve injury rat model of neuropathic pain, 21 days after surgery, we found increased TET1 expression in the medial prefrontal cortex and decreased expression in the caudate-putamen and the amygdala; TET2 was upregulated in the medial thalamus; TET3 mRNA levels were reduced in the medial prefrontal cortex and the caudate-putamen; and DNMT1 was downregulated in the caudate-putamen and the medial thalamus. No statistically significant changes in expression were observed with DNMT3a. Our results suggest a complex functional role for these genes in different brain areas in the context of neuropathic pain. The notion of DNA methylation and hydroxymethylation being cell-type specific and not tissue specific, as well as the possibility of chronologically differential gene expression after the establishment of neuropathic or inflammatory pain models, ought to be addressed in future studies.
LDL Affects the Immunomodulatory Response of Endothelial Cells by Modulation of the Promyelocytic Leukemia Protein (PML) Expression via PKC
Authors: Roos Kerrin , Berkholz Janine
Published: April 2023

In addition to its function as an intravascular lipid transporter, LDL also triggers signal transduction in endothelial cells (ECs), which, among other things, trigger immunomodulatory cascades, e.g., IL-6 upregulation. However, the molecular mechanisms of how these LDL-triggered immunological responses in ECs are realized are not fully understood. Since promyelocytic leukemia protein (PML) plays a role in promoting inflammatory processes, we examined the relationship between LDL, PML, and IL-6 in human ECs (HUVECs and EA.hy926 cells). RT-qPCR, immunoblotting, and immunofluorescence analyses showed that LDL but not HDL induced higher PML expression and higher numbers of PML-nuclear bodies (PML-NBs). Transfection of the ECs with a PML gene-encoding vector or PML-specific siRNAs demonstrated PML-regulated IL-6 and IL-8 expression and secretion after LDL exposure. Moreover, incubation with the PKC inhibitor sc-3088 or the PKC activator PMA showed that LDL-induced PKC activity leads to the upregulation of PML mRNA and PML protein. In summary, our experimental data suggest that high LDL concentrations trigger PKC activity in ECs to upregulate PML expression, which then increases production and secretion of IL-6 and IL-8. This molecular cascade represents a novel cellular signaling pathway with immunomodulatory effects in ECs in response to LDL exposure.
NMR-Relaxometric Investigation of Mn(II)-Doped Polyoxometalates in Aqueous Solutions
Authors: Korenev Vladimir S. , Burilova Evgenia A. , Volchek Victoria V. , Benassi Enrico , Amirov Rustem R. , Sokolov Maxim N. , Abramov Pavel A.
Published: April 2023

Solution behavior of K;5[(Mn(H2O))PW11O39]·7H2O (1), Na3.66(NH4)4.74H3.1[(MnII(H2O))2.75(WO(H2O))0.25(α-B-SbW9O33)2]·27H2O (2), and Na4.6H3.4[(MnII(H2O)3)2(WO2)2(β-B-TeW9O33)2]·19H2O (3) was studied with NMR-relaxometry and HPLC-ICP-AES (High Performance Liquid Chromatography coupled with Inductively Coupled Plasma Atomic Emission Spectroscopy). According to the data, the [(Mn(H2O))PW11O39]5− Keggin-type anion is the most stable in water among the tested complexes, even in the presence of ethylenediaminetetraacetic acid (EDTA) or diethylenetriaminepentaacetic acid (DTPA). Aqueous solutions of 2 and 3 anions are less stable and contain other species resulting from dissociation of Mn2+. Quantum chemical calculations show the change in Mn2+ electronic state between [Mn(H2O)6]2+ and [(Mn(H2O))PW11O39]5−.
Tff3−/− Knock-Out Mice with Altered Lipid Metabolism Exhibit a Lower Level of Inflammation following the Dietary Intake of Sodium Chloride for One Week
Authors: Kolobarić Nikolina , Mihalj Martina , Kozina Nataša , Matić Anita , Mihaljević Zrinka , Jukić Ivana , Drenjančević Ines
Published: April 2023

A high salt intake causes hemodynamic changes and promotes immune response through cell activation and cytokine production, leading to pro-inflammatory conditions. Transgenic Tff3−/− knock-out mice (TFF3ko) (n = 20) and wild-type mice (WT) (n = 20) were each divided into the (1) low-salt (LS) group and (2) high-salt (HS) group. Ten-week-old animals were fed with standard rodent chow (0.4% NaCl) (LS) or food containing 4% NaCl (HS) for one week (7 days). Inflammatory parameters from the sera were measured by Luminex assay. The integrin expression and rates of T cell subsets of interest from the peripheral blood leukocytes (PBLs) and mesenteric lymph nodes (MLNs) were measured using flow cytometry. There was a significant increase in high-sensitivity C reactive protein (hsCRP) only in the WT mice following the HS diet, while there were no significant changes in the serum levels of IFN-γ, TNF-α, IL-2, IL-4, or IL-6 as a response to treatment in either study groups. The rates of CD4+CD25+ T cells from MLNs decreased, while CD3+γδTCR+ from peripheral blood increased following the HS diet only in TFF3ko. γδTCR expressing T cell rates decreased in WT following the HS diet. The CD49d/VLA-4 expression decreased in the peripheral blood leukocytes in both groups following the HS diet. CD11a/LFA-1 expression significantly increased only in the peripheral blood Ly6C−CD11ahigh monocytes in WT mice following salt loading. In conclusion, salt-loading in knock-out mice caused a lower level of inflammatory response compared with their control WT mice due to gene depletion.
Chronic N-Acetyl-Cysteine Treatment Enhances the Expression of the Immediate Early Gene Nr4a1 in Response to an Acute Challenge in Male Rats: Comparison with the Antidepressant Venlafaxine
Authors: Brivio Paola , Gallo Maria Teresa , Gruca Piotr , Lason Magdalena , Litwa Ewa , Fumagalli Fabio , Papp Mariusz , Calabrese Francesca
Published: April 2023

Despite several antidepressant treatments being available in clinics, they are not effective in all patients. In recent years, N-acetylcysteine (NAC) has been explored as adjunctive therapy for many psychiatric disorders, including depression, for its antioxidant properties. Given the promising efficacy of this compound for the treatment of such pathologies, it is fundamental to investigate, at the preclinical level, the ability of the drug to act in the modulation of neuroplastic mechanisms in basal conditions and during challenging events in order to highlight the potential features of the drug useful for clinical efficacy. To this aim, adult male Wistar rats were treated with the antidepressant venlafaxine (VLX) (10 mg/kg) or NAC (300 mg/kg) for 21 days and then subjected to 1 h of acute restraint stress (ARS). We found that NAC enhanced the expression of several immediate early genes, markers of neuronal plasticity in the ventral and dorsal hippocampus, prefrontal cortex and amygdala, and in particular it mediated the acute-stress-induced upregulation of Nr4a1 expression more than VLX. These data suggested the ability of NAC to induce coping strategies to face external challenges, highlighting its potential for the improvement of neuroplastic mechanisms for the promotion of resilience, in particular via the modulation of Nr4a1.
Evidence of the Dysbiotic Effect of Psychotropics on Gut Microbiota and Capacity of Probiotics to Alleviate Related Dysbiosis in a Model of the Human Colon
Authors: Ait Chait Yasmina , Mottawea Walid , Tompkins Thomas A. , Hammami Riadh
Published: April 2023

Growing evidence indicates that non-antibiotic therapeutics significantly impact human health by modulating gut microbiome composition and metabolism. In this study, we investigated the impact of two psychotropic drugs, aripiprazole and (S)-citalopram, on gut microbiome composition and its metabolic activity, as well as the potential of probiotics to attenuate related dysbiosis using an ex vivo model of the human colon. After 48 h of fermentation, the two psychotropics demonstrated distinct modulatory effects on the gut microbiome. Aripiprazole, at the phylum level, significantly decreased the relative abundances of Firmicutes and Actinobacteria, while increasing the proportion of Proteobacteria. Moreover, the families Lachnospiraceae, Lactobacillaceae, and Erysipelotrichaceae were also reduced by aripiprazole treatment compared to the control group. In addition, aripiprazole lowered the levels of butyrate, propionate, and acetate, as measured by gas chromatography (GC). On the other hand, (S)-citalopram increased the alpha diversity of microbial taxa, with no differences observed between groups at the family and genus level. Furthermore, a probiotic combination of Lacticaseibacillus rhamnosus HA-114 and Bifidobacterium longum R0175 alleviated gut microbiome alterations and increased the production of short-chain fatty acids to a similar level as the control. These findings provide compelling evidence that psychotropics modulate the composition and function of the gut microbiome, while the probiotic can mitigate related dysbiosis.
Membrane Adaptations and Cellular Responses of Sulfolobus acidocaldarius to the Allylamine Terbinafine
Authors: Rao Alka , de Kok Niels A. W. , Driessen Arnold J. M.
Published: April 2023

Cellular membranes are essential for compartmentalization, maintenance of permeability, and fluidity in all three domains of life. Archaea belong to the third domain of life and have a distinct phospholipid composition. Membrane lipids of archaea are ether-linked molecules, specifically bilayer-forming dialkyl glycerol diethers (DGDs) and monolayer-forming glycerol dialkyl glycerol tetraethers (GDGTs). The antifungal allylamine terbinafine has been proposed as an inhibitor of GDGT biosynthesis in archaea based on radiolabel incorporation studies. The exact target(s) and mechanism of action of terbinafine in archaea remain elusive. Sulfolobus acidocaldarius is a strictly aerobic crenarchaeon thriving in a thermoacidophilic environment, and its membrane is dominated by GDGTs. Here, we comprehensively analyzed the lipidome and transcriptome of S. acidocaldarius in the presence of terbinafine. Depletion of GDGTs and the accompanying accumulation of DGDs upon treatment with terbinafine were growth phase-dependent. Additionally, a major shift in the saturation of caldariellaquinones was observed, which resulted in the accumulation of unsaturated molecules. Transcriptomic data indicated that terbinafine has a multitude of effects, including significant differential expression of genes in the respiratory complex, motility, cell envelope, fatty acid metabolism, and GDGT cyclization. Combined, these findings suggest that the response of S. acidocaldarius to terbinafine inhibition involves respiratory stress and the differential expression of genes involved in isoprenoid biosynthesis and saturation.
Identification and Clinical Significance of Pancreatic Cancer Stem Cells and Their Chemotherapeutic Drug Resistance
Authors: Kuo Yu-Chi , Kou Hao-Wei , Hsu Chih-Po , Lo Chih-Hong , Hwang Tsann-Long
Published: April 2023

Pancreatic cancer ranks in the 10th–11th position among cancers affecting men in Taiwan, besides being a rather difficult-to-treat disease. The overall 5-year survival rate of pancreatic cancer is only 5–10%, while that of resectable pancreatic cancer is still approximately 15–20%. Cancer stem cells possess intrinsic detoxifying mechanisms that allow them to survive against conventional therapy by developing multidrug resistance. This study was conducted to investigate how to overcome chemoresistance and its mechanisms in pancreatic cancer stem cells (CSCs) using gemcitabine-resistant pancreatic cancer cell lines. Pancreatic CSCs were identified from human pancreatic cancer lines. To determine whether CSCs possess a chemoresistant phenotype, the sensitivity of unselected tumor cells, sorted CSCs, and tumor spheroid cells to fluorouracil (5-FU), gemcitabine (GEM), and cisplatin was analyzed under stem cell conditions or differentiating conditions. Although the mechanisms underlying multidrug resistance in CSCs are poorly understood, ABC transporters such as ABCG2, ABCB1, and ABCC1 are believed to be responsible. Therefore, we measured the mRNA expression levels of ABCG2, ABCB1, and ABCC1 by real-time RT-PCR. Our results showed that no significant differences were found in the effects of different concentrations of gemcitabine on CSCs CD44+/EpCAM+ of various PDAC cell line cultures (BxPC-3, Capan-1, and PANC-1). There was also no difference between CSCs and non-CSCs. Gemcitabine-resistant cells exhibited distinct morphological changes, including a spindle-shaped morphology, the appearance of pseudopodia, and reduced adhesion characteristics of transformed fibroblasts. These cells were found to be more invasive and migratory, and showed increased vimentin expression and decreased E-cadherin expression. Immunofluorescence and immunoblotting experiments demonstrated increased nuclear localization of total β-catenin. These alterations are hallmarks of epithelial-to-mesenchymal transition (EMT). Resistant cells showed activation of the receptor protein tyrosine kinase c-Met and increased expression of the stem cell marker cluster of differentiation (CD) 24, CD44, and epithelial specific antigen (ESA). We concluded that the expression of the ABCG2 transporter protein was significantly higher in CD44+ and EpCAM+ CSCs of PDAC cell lines. Cancer stem-like cells exhibited chemoresistance. Gemcitabine-resistant pancreatic tumor cells were associated with EMT, a more aggressive and invasive phenotype of numerous solid tumors. Increased phosphorylation of c-Met may also be related to chemoresistance, and EMT and could be used as an attractive adjunctive chemotherapeutic target in pancreatic cancer.
Identification of Signature Genes of Dilated Cardiomyopathy Using Integrated Bioinformatics Analysis
Authors: Wu Zhimin , Wang Xu , Liang Hao , Liu Fangfang , Li Yingxuan , Zhang Huaxing , Wang Chunying , Wang Qiao
Published: April 2023

Dilated cardiomyopathy (DCM) is characterized by left ventricular or biventricular enlargement with systolic dysfunction. To date, the underlying molecular mechanisms of dilated cardiomyopathy pathogenesis have not been fully elucidated, although some insights have been presented. In this study, we combined public database resources and a doxorubicin-induced DCM mouse model to explore the significant genes of DCM in full depth. We first retrieved six DCM-related microarray datasets from the GEO database using several keywords. Then we used the “LIMMA” (linear model for microarray data) R package to filter each microarray for differentially expressed genes (DEGs). Robust rank aggregation (RRA), an extremely robust rank aggregation method based on sequential statistics, was then used to integrate the results of the six microarray datasets to filter out the reliable differential genes. To further improve the reliability of our results, we established a doxorubicin-induced DCM model in C57BL/6N mice, using the “DESeq2” software package to identify DEGs in the sequencing data. We cross-validated the results of RRA analysis with those of animal experiments by taking intersections and identified three key differential genes (including BEX1, RGCC and VSIG4) associated with DCM as well as many important biological processes (extracellular matrix organisation, extracellular structural organisation, sulphur compound binding, and extracellular matrix structural components) and a signalling pathway (HIF-1 signalling pathway). In addition, we confirmed the significant effect of these three genes in DCM using binary logistic regression analysis. These findings will help us to better understand the pathogenesis of DCM and may be key targets for future clinical management.
Interventional Oncology and Immuno-Oncology: Current Challenges and Future Trends
Authors: Posa Alessandro , Contegiacomo Andrea , Ponziani Francesca Romana , Punzi Ernesto , Mazza Giulia , Scrofani Annarita , Pompili Maurizio , Goldberg Shraga Nahum , Natale Luigi , Gasbarrini Antonio , Sala Evis , Iezzi Roberto
Published: April 2023

Personalized cancer treatments help to deliver tailored and biologically driven therapies for cancer patients. Interventional oncology techniques are able to treat malignancies in a locoregional fashion, with a variety of mechanisms of action leading to tumor necrosis. Tumor destruction determines a great availability of tumor antigens that can be recognized by the immune system, potentially triggering an immune response. The advent of immunotherapy in cancer care, with the introduction of specific immune checkpoint inhibitors, has led to the investigation of the synergy of these drugs when used in combination with interventional oncology treatments. The aim of this paper is to review the most recent advances in the field of interventional oncology locoregional treatments and their interactions with immunotherapy.
HP1γ Prevents Activation of the cGAS/STING Pathway by Preserving Nuclear Envelope and Genomic Integrity in Colon Adenocarcinoma Cells
Authors: Mata-Garrido Jorge , Frizzi Laura , Nguyen Thien , He Xiangyan , Chang-Marchand Yunhua , Xiang Yao , Reisacher Caroline , Casafont Iñigo , Arbibe Laurence
Published: April 2023

Chronic inflammatory processes in the intestine result in serious conditions such as inflammatory bowel disease (IBD) and cancer. An increased detection of cytoplasmic DNA sensors has been reported in the IBD colon mucosa, suggesting their contribution in mucosal inflammation. Yet, the mechanisms altering DNA homeostasis and triggering the activation of DNA sensors remain poorly understood. In this study, we show that the epigenetic regulator HP1γ plays a role in preserving nuclear envelope and genomic integrity in enterocytic cells, thereby protecting against the presence of cytoplasmic DNA. Accordingly, HP1 loss of function led to the increased detection of cGAS/STING, a cytoplasmic DNA sensor that triggers inflammation. Thus, in addition to its role as a transcriptional silencer, HP1γ may also exert anti-inflammatory properties by preventing the activation of the endogenous cytoplasmic DNA response in the gut epithelium.