bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Variation and Heritability of Sensory and Artisan Bread Traits in a Set of SRW Wheat Breeding Lines
Authors: Castellari Maria P. , Simsek Senay , Ohm Jae-Bom , Perry Robert , Poffenbarger Hanna J. , Phillips Timothy D. , Jacobsen Krista L. , Van Sanford David A.
Published: July 2023

Focus on local food production and supply chains has heightened in recent years, as evidenced and amplified by the COVID-19 pandemic. This study aimed to assess the suitability of soft red winter (SRW) wheat breeding lines for local artisan bakers interested in locally sourced, strong gluten wheat for bread. Seventy-six genotyped SRW wheat breeding lines were milled into whole wheat flour and baked into small loaves. Bread aroma, flavor, and texture were evaluated by a sensory panel, and bread quality traits, including sedimentation volume, dough extensibility, and loaf volume, were measured to estimate heritability. SE-HPLC was performed on white flour, and breeding lines were characterized for different protein fraction ratios. Heritability of loaf volume was moderately high (h2 = 0.68), while heritability of sedimentation volume, a much easier trait to measure, was slightly lower (h2 = 0.55). Certain protein fraction ratios strongly related to loaf volume had high heritability (h2 = 0.7). Even though only a moderate heritability estimate of dough extensibility was found in our study, high positive correlations were found between this parameter and sedimentation volume (r = 0.6) and loaf volume (r = 0.53). This low-input and highly repeatable parameter could be useful to estimate dough functionality characteristics. Flavor and texture heritability estimates ranged from 0.16 to 0.37, and the heritability estimate of aroma was not significantly different from zero. However, the sensorial characteristics were significantly correlated with each other, suggesting that we might be able to select indirectly for aroma by selecting for flavor or texture characteristics. From a genome-wide association study (GWAS), we identified six SNPs (single nucleotide polymorphisms) associated with loaf volume that could be useful in breeding for this trait. Producing high-quality strong gluten flour in our high rainfall environment is a challenge, but it provides local growers and end users with a value-added opportunity.
Are the Blueberries We Buy Good Quality? Comparative Study of Berries Purchased from Different Outlets
Authors: Sanchez-Ballesta M. Teresa , Marti-Anders Carmen , Álvarez M. Dolores , Escribano M. Isabel , Merodio Carmen , Romero Irene
Published: July 2023

Blueberries (Vaccinium corymbosum L.) are becoming increasingly popular for their nutritional and health benefits, and their economic value is therefore increasing. The loss of quality that can occur due to softening and fungal attack is an important consideration when marketing blueberries. Despite the added value of blueberries, no studies have been carried out on how the fruit arrives at the outlets just before purchase by the consumer in terms of firmness, physico-chemical parameters, phenolic compounds, and fungal growth. The aim of this work has been, therefore, to investigate possible differences in quality parameters between blueberries purchased from ten different outlets, regardless of the supplier. The results showed that all the samples were of acceptable quality, although they all had a low maturity index at the point of sale. None of the samples studied showed clear signs of fungal decay at the time of purchase, although we were able to grow and identify some pathogen specimens after cultivation. In terms of total phenolic and anthocyanin content, as well as antioxidant activity, all the samples showed low values, possibly due to their postharvest storage, but they were within the expected range for this fruit. On the other hand, differences in the measured parameters were observed between samples of the same cultivar while no differences were found between conventionally and organically grown blueberries. This suggests that preharvest (such as edaphoclimatic conditions, agricultural practices, and cultivars) and postharvest factors (such as treatments used, storage, and transport temperatures) could influence the berry quality when they reach the consumer.
Research Progress of Perfluoroalkyl Substances in Edible Oil—A Review
Authors: Han Yingyi , Cao Xueli
Published: July 2023

Perfluoroalkyl substances (PFASs) have been widely used in different types of consumer and industrial applications such as surfactants, household cleaning products, textiles, carpets, cosmetics, firefighting foams, and food packaging because of their good stability and special physicochemical properties of hydrophobicity, oleophobicity, high temperature resistance, etc. Meanwhile, PFASs are considered an emerging organic pollutant due to their persistence and potential toxicity to human health. PFASs occur in edible oil, an important component of the global diet, mainly in three ways: raw material contamination, process contamination, and migration from oil contact materials. Thus, the occurrence of PFAS in edible oils has drawn more and more attention in recent years. In this work, the pertinent literature of the last two decades from the Web of Science database was researched. This review systematically addressed the potential sources, the contamination levels, and the progress of the determination of PFASs in edible oil. It aims to provide a relatively whole profile of PFASs in edible oil, render assistance to minimise human exposure to PFASs, and standardise the detection methods of perfluoroalkyl substances in edible oil.
Blue Chambers, Bluebooks, and Contes Bleus: Gothic Terror and Female Deviance in Nineteenth-Century Adaptations of ‘Bluebeard’
Authors: Cabiati Alessandro
Published: July 2023

With its suspenseful atmosphere, mysterious and murderous male protagonist, and magical objects, it is hardly surprising that Charles Perrault’s conte bleu ‘La Barbe bleue’ (1697) was the inspiration for numerous Gothic tales in the nineteenth century. Some of these adaptations placed Gothic devices such as the representation of the terror experienced by Bluebeard’s latest wife within the broader nineteenth-century cultural discourse on female deviance, and its relations with masculine authority and dominance. By removing from the tale Perrault’s warning against female curiosity and imprudence and focusing on the wife’s feelings of fear and terror, these adaptations amplify the intrinsic Gothicism of the Bluebeard story, thus providing the female protagonist with a psychological depth that includes, as I demonstrate in this study, a display of a variety of abnormal behaviours. In these Gothic adaptations, the terror experienced by Bluebeard’s wife serves as a springboard for the representation of psychological and nervous disorders commonly diagnosed in the nineteenth century such as hysteria, monomania, female depravity, and masochism. Showing the interculturality and intermediality of these themes, this essay analyses rewritings of Perrault’s ‘Bluebeard’ from nineteenth-century Britain, France, and the United States, including Gothic bluebooks, poems, dramas, and short stories.
Indicators Related to Marital Dissatisfaction
Authors: Sánchez Claudia , Mota Cecilia
Published: July 2023

This is a study on indicators related to marital dissatisfaction. The research was conducted by the psychology department of a reproductive health institution in Mexico City. The objective was to know the relation between marital satisfaction/dissatisfaction and gender roles, self-esteem, the types of coping strategies and the types of violence perceived from the partner. It was a nonexperimental, retrospective, cross-sectional study of two samples—one of women and one of men—classified by marital satisfaction or dissatisfaction. The nonprobability quota sampling included 208 participants: 104 women and 104 men. Comparisons, correlations and a discriminant analysis were made to identify the most significant variables. Women with marital dissatisfaction perceived blackmail, psychological violence and humiliation/devaluation from their partner; they preferably adopt a submissive gender role and use escape/avoidance as a coping strategy, and so do the men with marital dissatisfaction, who also perceived blackmail, control and psychological violence from their partner; they have low self-esteem, and they preferably adopt a submissive gender role. Isolating factors will allow for more specificity in terms of psychological care at health institutions as well as avoiding gender biases and preventing an increase of violence in couples.
System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis
Authors: Patil Vishal S. , Harish Darasaguppe R. , Sampat Ganesh H. , Roy Subarna , Jalalpure Sunil S. , Khanal Pukar , Gujarathi Swarup S. , Hegde Harsha V.
Published: July 2023

Hepatitis B infection caused by the hepatitis B virus is a life-threatening cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Researchers have produced multiple in vivo models for hepatitis B virus (HBV) and, currently, there are no specific laboratory animal models available to study HBV pathogenesis or immune response; nonetheless, their limitations prevent them from being used to study HBV pathogenesis, immune response, or therapeutic methods because HBV can only infect humans and chimpanzees. The current study is the first of its kind to identify a suitable chemically induced liver cirrhosis/HCC model that parallels HBV pathophysiology. Initially, data from the peer-reviewed literature and the GeneCards database were compiled to identify the genes that HBV and seven drugs (acetaminophen, isoniazid, alcohol, D-galactosamine, lipopolysaccharide, thioacetamide, and rifampicin) regulate. Functional enrichment analysis was performed in the STRING server. The network HBV/Chemical, genes, and pathways were constructed by Cytoscape 3.6.1. About 1546 genes were modulated by HBV, of which 25.2% and 17.6% of the genes were common for alcohol and lipopolysaccharide-induced hepatitis. In accordance with the enrichment analysis, HBV activates the signaling pathways for apoptosis, cell cycle, PI3K-Akt, TNF, JAK-STAT, MAPK, chemokines, NF-kappa B, and TGF-beta. In addition, alcohol and lipopolysaccharide significantly activated these pathways more than other chemicals, with higher gene counts and lower FDR scores. In conclusion, alcohol-induced hepatitis could be a suitable model to study chronic HBV infection and lipopolysaccharide-induced hepatitis for an acute inflammatory response to HBV.
Multiplatform Metabolomics Characterization Reveals Novel Metabolites and Phospholipid Compositional Rules of Haemophilus influenzae Rd KW20
Authors: Fernández-García Miguel , Ares-Arroyo Manuel , Wedel Emilia , Montero Natalia , Barbas Coral , Rey-Stolle Mª Fernanda , González-Zorn Bruno , García Antonia
Published: July 2023

Haemophilus influenzae is a gram-negative bacterium of relevant clinical interest. H. influenzae Rd KW20 was the first organism to be sequenced and for which a genome-scale metabolic model (GEM) was developed. However, current H. influenzae GEMs are unable to capture several aspects of metabolome nature related to metabolite pools. To directly and comprehensively characterize the endometabolome of H. influenzae Rd KW20, we performed a multiplatform MS-based metabolomics approach combining LC-MS, GC-MS and CE-MS. We obtained direct evidence of 15–20% of the endometabolome present in current H. influenzae GEMs and showed that polar metabolite pools are interconnected through correlating metabolite islands. Notably, we obtained high-quality evidence of 18 metabolites not previously included in H. influenzae GEMs, including the antimicrobial metabolite cyclo(Leu-Pro). Additionally, we comprehensively characterized and evaluated the quantitative composition of the phospholipidome of H. influenzae, revealing that the fatty acyl chain composition is largely independent of the lipid class, as well as that the probability distribution of phospholipids is mostly related to the conditional probability distribution of individual acyl chains. This finding enabled us to provide a rationale for the observed phospholipid profiles and estimate the abundance of low-level species, permitting the expansion of the phospholipidome characterization through predictive probabilistic modelling.
Molecular Design of Magnetic Resonance Imaging Agents Binding to Amyloid Deposits
Authors: Nikiforova Alena , Sedov Igor
Published: July 2023

The ability to detect and monitor amyloid deposition in the brain using non-invasive imaging techniques provides valuable insights into the early diagnosis and progression of Alzheimer’s disease and helps to evaluate the efficacy of potential treatments. Magnetic resonance imaging (MRI) is a widely available technique offering high-spatial-resolution imaging. It can be used to visualize amyloid deposits with the help of amyloid-binding diagnostic agents injected into the body. In recent years, a number of amyloid-targeted MRI probes have been developed, but none of them has entered clinical practice. We review the advances in the field and deduce the requirements for the molecular structure and properties of a diagnostic probe candidate. These requirements make up the base for the rational design of MRI-active small molecules targeting amyloid deposits. Particular attention is paid to the novel cryo-EM structures of the fibril aggregates and their complexes, with known binders offering the possibility to use computational structure-based design methods. With continued research and development, MRI probes may revolutionize the diagnosis and treatment of neurodegenerative diseases, ultimately improving the lives of millions of people worldwide.
Isomers Recognition in HPLC-MS/MS Analysis of Human Plasma Samples by Using an Ion Trap Supported by a Linear Equations-Based Algorithm
Authors: Pallecchi Marco , Lucio Luigi , Braconi Laura , Menicatti Marta , Dei Silvia , Teodori Elisabetta , Bartolucci Gianluca
Published: July 2023

The tandem mass spectrometry (MS/MS) approach employing an ion trap mass analyzer (IT) was evaluated in isomers recognition. The proposed approach consists of sole, simple, and rapid liquid chromatographic separation (HPLC) without requiring resolution between the analytes. Then, the MS/MS properties were optimized to solve the signal assignment using post-processing data elaboration (LEDA). The IT-MS/MS experiment uses the same site, helium as collision gas, and different time steps to modify the applied conditions on the studied ions. Nevertheless, helium cannot ensure the quick energization of the precursor ion due to its small cross-section. Then, different combinations between excitation amplitude (ExA) and excitation time (ExT) were tested to achieve the activation of the fragmentation channels and the formation of the MS/MS spectrum. Usually, the IT-MS/MS acquisition cycle is longer for other multistage instruments, decreasing the frequency of sample data collection and influencing the chromatographic profile. To solve these problems, two time segments were set up, and the elution conditions were optimized with a compromise between peaks distinction and run time reduction. The developed HPLC-MS/MS method was checked and applied to analyze a series of human plasma samples spiked with an equimolar mixture of pair of isomers.
Comparison of Four Methods of RNA Extraction and cDNA Synthesis from The Venom of Peruvian Snakes of the Genus Bothrops of Clinical Importance
Authors: Torrejón Daniel , Cárdenas Javier , Juárez Diana , Espinoza Jordano , Proleón Alex , Agurto-Arteaga Andrés , Lazo Fanny , Leguía Mariana , Urra Félix A. , Sánchez Eladio F. , Chávez-Olortegui Carlos , Vivas-Ruiz Dan E. , Yarlequé Armando
Published: July 2023

RNA purification and cDNA synthesis represents the starting point for molecular analyses of snake venom proteins-enzymes. Usually, the sacrifice of snakes is necessary for venom gland extraction to identify protein-coding transcripts; however, the venom can be used as a source of transcripts. Although there are methods for obtaining RNA from venom, no comparative analysis has been conducted in the Bothrops genus. In the present study, we compared four commercial methods for RNA purification and cDNA synthesis from venom (liquid, lyophilized, or long-term storage) of four clinically relevant species of Peruvian Bothrops. Our results show that the TRIzol method presents the highest yield of RNA purified from venom (59 ± 11 ng/100 µL or 10 mg). The SuperScript First-Strand Synthesis System kit produced high amounts of cDNA (3.2 ± 1.2 ng cDNA/ng RNA), and the highest value was from combination with the Dynabeads mRNA DIRECT kit (4.8 ± 2.0 ng cDNA/ng RNA). The utility of cDNA was demonstrated with the amplification of six relevant toxins: thrombin-like enzymes, P-I and P-III metalloproteinases, acid and basic phospholipases A2, and disintegrins. To our knowledge, this is the first comparative study of RNA purification and cDNA synthesis methodologies from Bothrops genus venom.
Extracellular Matrix Expression in Human Pancreatic Fat Cells of Patients with Normal Glucose Regulation, Prediabetes and Type 2 Diabetes
Authors: Siegel-Axel Dorothea , Barroso Oquendo Morgana , Gerst Felicia , Fend Falko , Wagner Robert , Heni Martin , Königsrainer Alfred , Häring Hans-Ulrich , Fritsche Andreas , Schleicher Erwin , Birkenfeld Andreas L. , Stefan Norbert
Published: July 2023

Previously, we found that human pancreatic preadipocytes (PPAs) and islets influence each other and that the crosstalk with the fatty liver via the hepatokine fetuin-A/palmitate induces inflammatory responses. Here, we examined whether the mRNA-expression of pancreatic extracellular matrix (ECM)-forming and -degrading components differ in PPAs from individuals with normal glucose regulation (PPAs-NGR), prediabetes (PPAs-PD), and type 2 diabetes (PPAs-T2D), and whether fetuin-A/palmitate impacts ECM-formation/degradation and associated monocyte invasion. Human pancreatic resections were analyzed (immuno)histologically. PPAs were studied for mRNA expression by real-time PCR and protein secretion by Luminex analysis. Furthermore, co-cultures with human islets and monocyte migration assays in Transwell plates were conducted. We found that in comparison with NGR-PPAs, TIMP-2 mRNA levels were lower in PPAs-PD, and TGF-β1 mRNA levels were higher in PPAs-T2D. Fetuin-A/palmitate reduced fibronectin, decorin, TIMP-1/-2 and TGF-ß1 mRNA levels. Only fibronectin was strongly downregulated by fetuin-A/palmitate independently of the glycemic status. Co-culturing of PPAs with islets increased TIMP-1 mRNA expression in islets. Fetuin-A/palmitate increased MMP-1, usherin and dermatopontin mRNA-levels in co-cultured islets. A transmigration assay showed increased monocyte migration towards PPAs, which was enhanced by fetuin-A/palmitate. This was more pronounced in PPAs-T2D. The expression of distinct ECM components differs in PPAs-PD and PPAs-T2D compared to PPAs-NGR, suggesting that ECM alterations can occur even in mild hyperglycemia. Fetuin-A/palmitate impacts on ECM formation/degradation in PPAs and co-cultured islets. Fetuin-A/palmitate also enhances monocyte migration, a process which might impact on matrix turnover.
Integrated Analysis of Transcriptomics and Metabolomics Unveil the Novel Insight of One-Year-Old Precocious Mechanism in the Chinese Mitten Crab, Eriocheir sinensis
Authors: Wang Lanmei , Gao Jiancao , Cao Xi , Du Jinliang , Cao Liping , Nie Zhijuan , Xu Gangchun , Dong Zaijie
Published: July 2023

Eriocheir sinensis is traditionally a native high-value crab that is widely distributed in eastern Asia, and the precocity is considered the bottleneck problem affecting the development of the industry. The precocious E. sinensis is defined as a crab that reaches complete sexual maturation during the first year of its lifespan rather than as normally in the second year. However, the exact regulatory mechanisms underlying the precocity are still unclear to date. This study is the first to explore the mechanism of precocity with transcriptome-metabolome association analysis between the precocious and normal sexually mature E. sinensis. Our results indicated that the phenylalanine metabolism (map00360) and neuroactive ligand-receptor interaction (map04080) pathways play an important role in the precocity in the ovary of E. sinensis. In map00360, the predicted aromatic-L-amino-acid decarboxylase and 4-hydroxyphenylpyruvate dioxygenase isoform X1 genes and the phenethylamine, phenylethyl alcohol, trans-2-hydroxycinnamate, and L-tyrosine metabolites were all down-regulated in the ovary of the precocious E. sinensis. The map04080 was the common KEGG pathway in the ovary and hepatopancreas between the precocious and normal crab. In the ovary, the predicted growth hormone secretagogue receptor type 1 gene was up-regulated, and the L-glutamate metabolite was down-regulated in the precocious E. sinensis. In the hepatopancreas, the predicted forkhead box protein I2 gene and taurine metabolite were up-regulated and the the L-glutamate metabolite was down-regulated in the precocious crab. There was no common pathway in the testis. Numerous common pathways in the hepatopancreas between male precocious and normal crab were identified. The specific amino acids, fatty acids and flavorful nucleotide (inosine monophosphate (MP), cytidine MP, adenosine MP, uridine MP, and guanosine MP) contents in the hepatopancreas and gonads further confirmed the above omics results. Our results suggest that the phenylalanine metabolism may affect the ovarian development by changing the contents of the neurotransmitter and tyrosine. The neuroactive ligand–receptor interaction pathway may affect the growth by changing the expressions of related genes and affect the umami taste of the gonads and hepatopancreas through the differences of L-glutamate metabolite in the precocious E. sinensis. The results provided valuable and novel insights on the precocious mechanism and may have a significant impact on the development of the E. sinensis aquaculture industry.
Tumor-Suppressive and Immunomodulating Activity of miR-30a-3p and miR-30e-3p in HNSCC Cells and Tumoroids
Authors: Conrad Ombline , Burgy Mickaël , Foppolo Sophie , Jehl Aude , Thiéry Alicia , Guihard Sébastien , Vauchelles Romain , Jung Alain C. , Mourtada Jana , Macabre Christine , Ledrappier Sonia , Chenard Marie-Pierre , Onea Mihaela-Alina , Danic Aurélien , Dourlhes Thomas , Thibault Claire , Schultz Philippe , Dontenwill Monique , Martin Sophie
Published: July 2023

Head and neck squamous cell carcinomas (HNSCCs) are heterogeneous tumors, well known for their frequent relapsing nature. To counter recurrence, biomarkers for early diagnosis, prognosis, or treatment response prediction are urgently needed. miRNAs can profoundly impact normal physiology and enhance oncogenesis. Among all of the miRNAs, the miR-30 family is frequently downregulated in HNSCC. Here, we determined how levels of the 3p passenger strands of miR-30a and miR-30e affect tumor behavior and clarified their functional role in LA-HNSCC. In a retrospective study, levels of miR-30a-3p and miR-30e-3p were determined in 110 patients and correlated to overall survival, locoregional relapse, and distant metastasis. miR-30a/e-3p were expressed in HNSCC cell lines and HNSCC patient-derived tumoroids (PDTs) to investigate their effect on tumor cells and their microenvironment. Both miRNAs were found to have a prognosis value since low miR-30a/e-3p expression correlates to adverse prognosis and reduces overall survival. Low expression of miR-30a/e-3p is associated with a shorter time until locoregional relapse and a shorter time until metastasis, respectively. miR-30a/e-3p expression downregulates both TGF-βR1 and BMPR2 and attenuates the survival and motility of HNSCC. Results were confirmed in PDTs. Finally, secretomes of miR-30a/e-3p-transfected HNSCC activate M1-type macrophages, which exert stronger phagocytic activities toward tumor cells. miR-30a/e-3p expression can discriminate subgroups of LA-HNSCC patients with different prognosis, making them good candidates as prognostic biomarkers. Furthermore, by targeting members of the TGF-β family and generating an immune-permissive microenvironment, they may emerge as an alternative to anti-TGF-β drugs to use in combination with immune checkpoint inhibitors.
The Prognostic Significance of Tumor-Infiltrating Lymphocytes, PD-L1, BRCA Mutation Status and Tumor Mutational Burden in Early-Stage High-Grade Serous Ovarian Carcinoma—A Study by the Spanish Group for Ovarian Cancer Research (GEICO)
Authors: Pizarro David , Romero Ignacio , Pérez-Mies Belén , Redondo Andrés , Caniego-Casas Tamara , Carretero-Barrio Irene , Cristóbal Eva , Gutiérrez-Pecharromán Ana , Santaballa Ana , D’Angelo Emanuela , Hardisson David , Vieites Begoña , Matías-Guiu Xavier , Estévez Purificación , Guerra Eva , Prat Jaime , Poveda Andrés , López-Guerrero José Antonio , Palacios José
Published: July 2023

Early stages are under-represented in studies on the molecular and immune features of high-grade serous ovarian carcinoma (HGSOC), and specific studies focused on early-stage HGSOC are required for a better prognostic stratification and to personalize chemotherapy. The aim of this study was to determine the prognostic significance of CD8+ and CD4+ tumor-infiltrating lymphocytes (TILs), tumoral cell PD-L1 expression, BRCA mutational status and tumor mutation burden (TMB) in early-stage HGSOC. A retrospective study was performed on stage I and II HGSOC from the Molecular Reclassification of Early Stages of Ovarian Cancer (RECLAMO) cohort from the Spanish Group of Ovarian Cancer Research (GEICO). Centralized histological typing was performed based on morphological and immunohistochemical features. Intraepithelial (i) and stromal (s) CD8+ and CD4+ T cells and PD-L1 were evaluated on tissue microarrays by immunohistochemistry. BRCA1 and BRCA2 mutation status and TMB were analyzed in tumor DNA using next-generation sequencing. The study included 124 tumors. High iCD8+ (>20 TILs/core), low/intermediate CD4+ (<20 TILs/core) and high CD8+/CD4+ ratio (>35/core) were associated with favorable outcomes. Tumor cell PD-L1 expression (TPS ≥ 1) was present in only 8% of tumors. In total, 11 (16%) and 6 (9%) out of 69 HGSOC tested carried pathogenic or likely pathogenic BRCA1 or BRCA2 mutations, respectively. Median TMB of 40 tumors analyzed was 5.04 mutations/Mb and only 6 tumors had 10 or more mutations/Mb. BRCA status and TMB were not associated with TILs or prognosis. When compared with studies on advanced HGSOC, our results suggested that prognostic variables differed according to stage and that more studies focused on early stages of HGSOC are needed to better stratify these tumors.
Analysis of Raffinose Synthase Gene Family in Bread Wheat and Identification of Drought Resistance and Salt Tolerance Function of TaRS15-3B
Authors: Guo Jiagui , Yang Yan , Wang Tingting , Wang Yizhen , Zhang Xin , Min Donghong , Zhang Xiaohong
Published: July 2023

Raffinose synthase (RS) plays a crucial role in plant growth and development, as well as in responses to biotic stresses and abiotic stresses, yet few studies have been conducted on its role in bread wheat. Therefore, in this study we screened and identified a family of bread wheat raffinose synthase genes based on bread wheat genome information and analyzed their physicochemical properties, phylogenetic evolutionary relationships, conserved structural domains, promoter cis-acting elements, and expression patterns. The BSMV-induced silencing of TaRS15-3B resulted in the bread wheat seedlings being susceptible to drought and salt stress and reduced the expression levels of stress-related and ROS-scavenging genes in bread wheat plants. This further affected the ability of bread wheat to cope with drought and salt stress. In conclusion, this study revealed that the RS gene family in bread wheat plays an important role in plant response to abiotic stresses and that the TaRS15-3B gene can improve the tolerance of transgenic bread wheat to drought and salt stresses, provide directions for the study of other RS gene families in bread wheat, and supply candidate genes for use in molecular breeding of bread wheat for stress resistance.
CRISPR/Cas9-Mediated Cytosine Base Editing Using an Improved Transformation Procedure in Melon (Cucumis melo L.)
Authors: Shirazi Parsa Hadi , Sabet Mohammad Sadegh , Moieni Ahmad , Shojaeiyan Abdolali , Dogimont Catherine , Boualem Adnane , Bendahmane Abdelhafid
Published: July 2023

Melon is a recalcitrant plant for stable genetic transformation. Various protocols have been tried to improve melon transformation efficiency; however, it remains significantly low compared to other plants such as tomato. In this study, the primary focus was on the optimization of key parameters during the inoculation and co-culture steps of the genetic transformation protocol. Our results showed that immersing the explants in the inoculation medium for 20 min significantly enhanced transformation efficiency. During the co-culture step, the use of filer paper, 10 mM 2-(N-morpholino)-ethanesulfonic acid (MES), and a temperature of 24 °C significantly enhanced the melon transformation efficiency. Furthermore, the impact of different ethylene inhibitors and absorbers on the transformation efficiency of various melon varieties was explored. Our findings revealed that the use of these compounds led to a significant improvement in the transformation efficiency of the tested melon varieties. Subsequently, using our improved protocol and reporter-gene construct, diploid transgenic melons successfully generated. The efficiency of plant genetic transformation ranged from 3.73 to 4.83%. Expanding the scope of our investigation, the optimized protocol was applied to generate stable gene-edited melon lines using the Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-mediated cytosine base editor and obtained melon lines with editions (C-to-T and C-to-G) in the eukaryotic translation initiation factor 4E, CmeIF4E gene. In conclusion, the optimized melon transformation protocol, along with the utilization of the CRISPR/Cas9-mediated cytosine base editor, provides a reliable framework for functional gene engineering in melon. These advancements hold significant promise for furthering genetic research and facilitating crop improvement in this economically important plant species.
Vitamin E and Its Molecular Effects in Experimental Models of Neurodegenerative Diseases
Authors: da Cunha Germano Bianca Caroline , de Morais Lara Cristina Carlos , Idalina Neta Francisca , Fernandes Amélia Carolina Lopes , Pinheiro Francisco Irochima , do Rego Amália Cinthia Meneses , Araújo Filho Irami , de Azevedo Eduardo Pereira , de Paiva Cavalcanti José Rodolfo Lopes , Guzen Fausto Pierdona , Cobucci Ricardo Ney
Published: July 2023

With the advancement of in vivo studies and clinical trials, the pathogenesis of neurodegenerative diseases has been better understood. However, gaps still need to be better elucidated, which justifies the publication of reviews that explore the mechanisms related to the development of these diseases. Studies show that vitamin E supplementation can protect neurons from the damage caused by oxidative stress, with a positive impact on the prevention and progression of neurodegenerative diseases. Thus, this review aims to summarize the scientific evidence of the effects of vitamin E supplementation on neuroprotection and on neurodegeneration markers in experimental models. A search for studies published between 2000 and 2023 was carried out in the PubMed, Web of Science, Virtual Health Library (BVS), and Embase databases, in which the effects of vitamin E in experimental models of neurodegeneration were investigated. A total of 5669 potentially eligible studies were identified. After excluding the duplicates, 5373 remained, of which 5253 were excluded after checking the titles, 90 articles after reading the abstracts, and 11 after fully reviewing the manuscripts, leaving 19 publications to be included in this review. Experiments with in vivo models of neurodegenerative diseases demonstrated that vitamin E supplementation significantly improved memory, cognition, learning, motor function, and brain markers associated with neuroregeneration and neuroprotection. Vitamin E supplementation reduced beta-amyloid (Aβ) deposition and toxicity in experimental models of Alzheimer’s disease. In addition, it decreased tau-protein hyperphosphorylation and increased superoxide dismutase and brain-derived neurotrophic factor (BDNF) levels in rodents, which seems to indicate the potential use of vitamin E in preventing and delaying the progress of degenerative lesions in the central nervous system.
Hypoxia Treatment of Adipose Mesenchymal Stem Cells Promotes the Growth of Dermal Papilla Cells via HIF-1α and ERK1/2 Signaling Pathways
Authors: Wang Qing , Zhou Mei , Zhang Hongyan , Hou Zhuang , Liu Dongjun
Published: July 2023

Dermal papilla cells (DPCs) cultured in vitro induce hair follicle formation. Using a hypoxic microenvironment to culture adipose mesenchymal stem cells (ADSCs) can promote hair follicle growth. However, the exact molecular mechanisms underlying this process remain unclear. In this study, ADSCs and DPCs from Arbas Cashmere goats were used. A hypoxic microenvironment promoted the proliferation of ADSCs and increased the pluripotency of ADSCs. The growth factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF) were upregulated in ADSCs in the hypoxia-conditioned medium (Hypo-cm). Hypo-cm also enhanced the ability of DPCs to induce hair follicle formation. Inhibitors of the ERK1/2 signaling pathway caused the expressions of growth factors that increased in hypoxic microenvironments to decrease; moreover, hypoxia-inducible factor-1α (HIF-1α) increased the expression levels of VEGF, bFGF, and PDGF and inhibited the expression of bone morphogenic protein 7 (BMP7). In conclusion, these findings improve the theoretical basis for the development of gene therapy drugs for the treatment of alopecia areata and hair thinning.
cGMP Signaling in Photoreceptor Degeneration
Authors: Li Shujuan , Ma Hongwei , Yang Fan , Ding Xiqin
Published: July 2023

Photoreceptors in the retina are highly specialized neurons with photosensitive molecules in the outer segment that transform light into chemical and electrical signals, and these signals are ultimately relayed to the visual cortex in the brain to form vision. Photoreceptors are composed of rods and cones. Rods are responsible for dim light vision, whereas cones are responsible for bright light, color vision, and visual acuity. Photoreceptors undergo progressive degeneration over time in many hereditary and age-related retinal diseases. Despite the remarkable heterogeneity of disease-causing genes, environmental factors, and pathogenesis, the progressive death of rod and cone photoreceptors ultimately leads to loss of vision/blindness. There are currently no treatments available for retinal degeneration. Cyclic guanosine 3′, 5′-monophosphate (cGMP) plays a pivotal role in phototransduction. cGMP governs the cyclic nucleotide-gated (CNG) channels on the plasma membrane of the photoreceptor outer segments, thereby regulating membrane potential and signal transmission. By gating the CNG channels, cGMP regulates cellular Ca2+ homeostasis and signal transduction. As a second messenger, cGMP activates the cGMP-dependent protein kinase G (PKG), which regulates numerous targets/cellular events. The dysregulation of cGMP signaling is observed in varieties of photoreceptor/retinal degenerative diseases. Abnormally elevated cGMP signaling interferes with various cellular events, which ultimately leads to photoreceptor degeneration. In line with this, strategies to reduce cellular cGMP signaling result in photoreceptor protection in mouse models of retinal degeneration. The potential mechanisms underlying cGMP signaling-induced photoreceptor degeneration involve the activation of PKG and impaired Ca2+ homeostasis/Ca2+ overload, resulting from overactivation of the CNG channels, as well as the subsequent activation of the downstream cellular stress/death pathways. Thus, targeting the cellular cGMP/PKG signaling and the Ca2+-regulating pathways represents a significant strategy for photoreceptor protection in retinal degenerative diseases.
Metal Hydride Hydrogen Storage (Compression) Units Operating at Near-Atmospheric Pressure of the Feed H2
Authors: Tarasov Boris , Arbuzov Artem , Mozhzhukhin Sergey , Volodin Aleksey , Fursikov Pavel , Davids Moegamat Wafeeq , Adeniran Joshua , Lototskyy Mykhaylo
Published: July 2023

Metal hydride (MH) hydrogen storage and compression systems with near-atmospheric H2 suction pressure are necessary for the utilization of the low-pressure H2 produced by solid oxide electrolyzers or released as a byproduct of chemical industries. Such systems should provide reasonably high productivity in the modes of both charge (H2 absorption at PL ≤ 1 atm) and discharge (H2 desorption at PH = 2–5 atm), which implies the provision of H2 equilibrium pressures Peq < PL at the available cooling temperature (TL = 15–20 °C) and, at the same time, Peq > PH when heated to TH = 90–150 °C. This work presents results of the development of such systems based on AB5-type intermetallics characterized by Peq of 0.1–0.3 atm and 3–8 atm for H2 absorption at TL = 15 °C and H2 desorption at TH = 100 °C, respectively. The MH powders mixed with 1 wt.% of Ni-doped graphene-like material or expanded natural graphite for the improvement of H2 charge dynamics were loaded in a cylindrical container equipped with internal and external heat exchangers. The developed units with a capacity of about 1 Nm3 H2 were shown to exhibit H2 flow rates above 10 NL/min during H2 charge at ≤1 atm when cooled to ≤20 °C with cold water and H2 release at a pressure above 2 and 5 atm when heated to 90 and 120 °C with hot water and steam, respectively.
Evolution of National Guidelines on Medicines Used to Treat COVID-19 in Pregnancy in 2020–2022: A Scoping Review
Authors: Maisonneuve Emeline , de Bruin Odette , Favre Guillaume , Goncé Anna , Donati Serena , Engjom Hilde , Hurley Eimir , Al-Fadel Nouf , Siiskonen Satu , Bloemenkamp Kitty , Nordeng Hedvig , Sturkenboom Miriam , Baud David , Panchaud Alice
Published: July 2023

The lack of inclusion of pregnant women in clinical trials evaluating the effectiveness of medicines to treat COVID-19 has made it difficult to establish evidence-based treatment guidelines for pregnant women. Our aim was to provide a review of the evolution and updates of the national guidelines on medicines used in pregnant women with COVID-19 published by the obstetrician and gynecologists’ societies in thirteen countries in 2020–2022. Based on the results of the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, the national societies successively recommended against prescribing hydroxychloroquine, lopinavir–ritonavir and azithromycin. Guidelines for remdesivir differed completely between countries, from compassionate or conditional use to recommendation against. Nirmatrelvir–ritonavir was authorized in Australia and the UK only in research settings and was no longer recommended in the UK at the end of 2022. After initial reluctance to use corticosteroids, the results of the RECOVERY trial have enabled the recommendation of dexamethasone in case of severe COVID-19 since mid-2020. Some societies recommended prescribing tocilizumab to pregnant patients with hypoxia and systemic inflammation from June 2021. Anti-SARS-CoV-2 monoclonal antibodies were authorized at the end of 2021 with conditional use in some countries, and then no longer recommended in Belgium and the USA at the end of 2022. The gradual convergence of the recommendations, although delayed compared to the general population, highlights the importance of the inclusion of pregnant women in clinical trials and of international collaboration to improve the pharmacological treatment of pregnant women with COVID-19.
Association of ADP-Induced Whole-Blood Platelet Aggregation with Serum Low-Density Lipoprotein Cholesterol in Patients with Coronary Artery Disease When Receiving Maintenance Ticagrelor-Based Dual Antiplatelet Therapy
Authors: Chyrchel Bernadeta , Kruszelnicka Olga , Wieczorek-Surdacka Ewa , Surdacki Andrzej
Published: July 2023

The degree of platelet inhibition in patients undergoing dual antiplatelet therapy (DAPT) affects cardiovascular outcomes after acute coronary syndromes (ACS) and/or percutaneous coronary intervention. Our aim was to search for correlates of residual ex vivo platelet reactivity and circulating soluble P-selectin (sP-selectin), an index of in vivo platelet activation, in patients being treated by DAPT with ticagrelor. Adenosine diphosphate (ADP)-induced platelet aggregability (by multiple electrode aggregometry) and plasma sP-selectin were estimated in 62 stable post-ACS subjects (46 men and 16 women; mean age: 64 ± 10 years; 30 with type 2 diabetes (T2DM)) undergoing maintenance DAPT with ticagrelor and aspirin. These patients did not exhibit heart failure or other relevant coexistent diseases except for properly controlled T2DM, mild renal insufficiency, and hypertension. We also assessed this in 64 subjects on clopidogrel-based DAPT matched for age, sex, and T2DM status. ADP-induced platelet aggregation was below the optimal levels (190–460 arbitrary units (AU) * min) in most patients receiving ticagrelor-based DAPT, especially in those with below-median (<1.9 mmol/L) serum concentrations of low-density lipoprotein cholesterol (LDL-c) (128 ± 61 vs. 167 ± 73 AU * min for below-median and above-median LDL-c, respectively, p = 0.025). In contrast, platelet reactivity did not differ by LDL-c on clopidogrel-based DAPT (246 ± 101 vs. 268 ± 108 AU * min for below-median and above-median LDL-c, respectively, p > 0.4). Plasma sP-selectin was found to be unrelated to serum LDL-c when receiving DAPT with ticagrelor (p > 0.4) or clopidogrel (p > 0.8). In conclusion, our preliminary observational study suggests the association of lower residual ex vivo platelet aggregability with better LDL-c control in patients undergoing ticagrelor-based maintenance DAPT, which does not appear to be reflected by plasma sP-selectin. Whether the serum LDL-c level should be considered among the factors affecting the degree of platelet inhibition for those treated with ticagrelor-based DAPT needs to be investigated in larger studies.
Clinical Network Systems Biology: Traversing the Cancer Multiverse
Authors: Mambetsariev Isa , Fricke Jeremy , Gruber Stephen B. , Tan Tingting , Babikian Razmig , Kim Pauline , Vishnubhotla Priya , Chen Jianjun , Kulkarni Prakash , Salgia Ravi
Published: July 2023

In recent decades, cancer biology and medicine have ushered in a new age of precision medicine through high-throughput approaches that led to the development of novel targeted therapies and immunotherapies for different cancers. The availability of multifaceted high-throughput omics data has revealed that cancer, beyond its genomic heterogeneity, is a complex system of microenvironments, sub-clonal tumor populations, and a variety of other cell types that impinge on the genetic and non-genetic mechanisms underlying the disease. Thus, a systems approach to cancer biology has become instrumental in identifying the key components of tumor initiation, progression, and the eventual emergence of drug resistance. Through the union of clinical medicine and basic sciences, there has been a revolution in the development and approval of cancer therapeutic drug options including tyrosine kinase inhibitors, antibody–drug conjugates, and immunotherapy. This ‘Team Medicine’ approach within the cancer systems biology framework can be further improved upon through the development of high-throughput clinical trial models that utilize machine learning models, rapid sample processing to grow patient tumor cell cultures, test multiple therapeutic options and assign appropriate therapy to individual patients quickly and efficiently. The integration of systems biology into the clinical network would allow for rapid advances in personalized medicine that are often hindered by a lack of drug development and drug testing.
Prediction of Posterior-to-Anterior Corneal Curvature Radii Ratio in Myopic Patients after LASIK, SMILE, and PRK Using Multivariate Regression Analysis
Authors: Cha David , Moshirfar Majid , Herron Michael , Santos Jordan , Hoopes Phillip
Published: July 2023

The ratio of posterior-to-anterior curvature radii of the cornea (P/A ratio) is an important element in determining corneal refractive power. P/A ratio has been well studied in patients prior to undergoing refractive surgery, but its postoperative value remains less so. We aimed to examine the value of preoperative characteristics of refractive surgery patients in predicting the 1-year postoperative P/A ratio in LASIK, PRK, and SMILE using both linear and multivariate regression analyses. This was a retrospective study that included patients with manifest refraction spherical equivalents (MRSE) from −7.71D to −0.25D. In total, 164 eyes underwent LASIK, 183 underwent PRK, and 46 underwent SMILE. All patients had preoperative and 1-year postoperative front sagittal and back sagittal keratometry measurements at 4, 5, and 6 mm around the corneal vertex. Postoperative P/A after LASIK, PRK, and SMILE was found to be significantly correlated with MRSE and preoperative P/A. Stepwise variable selection in multivariate regression revealed that spherical equivalent was the most significant predictor of postoperative P/A. When coupled with other preoperative characteristics, including P/A, age, asphericity, and keratometry, the multivariate regressions were able to produce models with high predictive value in LASIK (adjusted R2: 0.957), PRK (adjusted R2: 0.934), and SMILE (adjusted R2: 0.894).
Image Clarity Affects Tip-of-the-Tongue Rates for Faces
Authors: Lee Hyeonjeong , Pournaghdali Ali , Schwartz Bennett L.
Published: July 2023

Tip-of-the-tongue states are subjective experiences that unrecalled target words will be remembered. This study investigates if the visual fluency of familiar faces affects the likelihood of tip-of-the-tongue experiences (TOTs) as well as name recall and name recognition. To manipulate visual fluency, three levels of clarity for 396 celebrity faces were set: high, medium, and low clarity. Four hundred and twenty-nine participants were asked to recall the last names of the celebrities for all clarity levels, and, if they did not recall, to indicate if they experienced a TOT. Following the TOT question, they performed a name recognition test. Results showed that higher-clarity faces resulted in higher TOT rates than lower-clarity faces for unrecalled faces. Name recall was also higher for clearer faces. However, clarity level did not affect the correct answer rate on the name recognition test. These results support the view that perceptual cue-based factors influence TOT experiences.