bluuebunny/crossref_metadata_2025 huggingface dataset:
European DEMO Fusion Reactor: Design and Integration of the Breeding Blanket Feeding Pipes
Authors: Mozzillo Rocco , Vorpahl Christian , Bachmann Christian , Hernández Francisco A. , Del Nevo Alessandro
Published: June 2023

This article describes the design and configuration of the DEMO Breeding Blanket (BB) feeding pipes inside the upper port. As large BB segments require periodic replacement via the upper vertical ports, the space inside the upper port needs to be maximized. At the same time, the size of the upper port is constrained by the available space in between the toroidal field coils and the required space to integrate a thermal shield between the vacuum vessel (VV) port and the coils. The BB feeding pipes inside the vertical port need to be removed prior to BB maintenance, as they obstruct the removal kinematics. Since they are connected to the BB segments on the top and far from their vertical support on the bottom, the pipes need to be sufficiently flexible to allow for the thermal expansion of the BB segments and the pipes themselves. The optimization and verification of these BB pipes inside the upper port design are critical aspects in the development of DEMO. This article presents the chosen pipe configuration for both BB concepts considered for DEMO (helium- and water-cooled) and their structural verification for some of the most relevant thermal conditions. A 3D model of the pipes forest, both for the Helium-Cooled Pebble Bed (HCPB) and Water-Cooled Lithium Lead (WCLL) concepts, has been developed and integrated inside the DEMO Upper Port (UP), Upper Port Ring Channel, and Upper Port Annex (UPA). A preliminary structural analysis of the pipeline was carried out to check the structural integrity of the pipes, their flexibility against the thermal load, their internal pressure, and the deflection induced by the thermal expansion of the BB segments. The results showed that the secondary stress on the hot leg of the HCPB pipeline was above the limit, suggesting future improvements in its shape to increase the flexibility. Moreover, the WCLL concept did not have a critical point in terms of the secondary stress on the pipeline, since the thicknesses and the diameters of these pipes were smaller than the HCPB ones.
Effect of SPWM Inverter in Combination with Solar Uninterruptible Induction Motor Drive
Authors: Boros Ruben Rafael , Bodnár István
Published: June 2023

The increase in the popularity of uninterruptible induction motor drives has prompted industrial applications to be interested in this technology. Each of these drives has a rectifier at the input that charges batteries. When there is a power outage, an inverter powered by the batteries supplies the motor with electricity. In addition, a separate system of uninterruptible power supplies is regularly installed on the industrial site. The study highlights the advantages of combining the two systems and demonstrates them with simulation and measurement results. This paper will consider connecting solar panels to combined uninterruptible power systems. Solar panels can be used to charge batteries with high efficiency, requiring only MPPT controllers. Hence, if solar panels are installed on the roofs of industrial facilities, they can be integrated into the uninterruptible power supply. The paper describes the effects of combining an uninterruptible motor drive with a single-phase inverter that mainly affects the DC bus voltage. In turn, the DC bus voltage ripple and fluctuation also affects the quality parameters of the motor and single-phase load such as the Total Harmonic Distortion. Furthermore, the paper presents the solar-assisted combined system components used for the measurement, and the results derived from them.
Automatic Control of Chemolithotrophic Cultivation of Cupriavidus necator: Optimization of Oxygen Supply for Enhanced Bioplastic Production
Authors: Lambauer Vera , Permann Alexander , Petrášek Zdeněk , Subotić Vanja , Hochenauer Christoph , Kratzer Regina , Reichhartinger Markus
Published: June 2023

Gas fermentation is an upcoming technology to convert gaseous substrates into value-added products using autotrophic microorganisms. The hydrogen-oxidizing bacteria Cupriavidus necator efficiently uses CO2 as its sole carbon source, H2 as electron donor and O2 as electron acceptor. Surplus CO2 is stored in microbial storage material poly-(R)-3-hydroxybutyrate. O2 supply is the most critical parameter for growth and poly-(R)-3-hydroxybutyrate formation. A narrow O2 optimum between ~0.2 and ~4 mg/L was previously reported. Here, a standard benchtop bioreactor was redesigned for autotrophic growth of C. necator on explosive mixtures of CO2, H2 and O2. The bioreactor was equipped with mass flow control units and O2 and CO2 sensors. A controller for automated gas dosage based on a mathematical model including gas mass transfer, gas consumption and sensor response time was developed. Dissolved O2 concentrations were adjusted with high precision to 1, 2 and 4% O2 saturation (0.4, 0.8 and 1.5 mg/L dissolved O2, respectively). In total, up to 15 g/L cell dry weight were produced. Residual biomass formation was 3.6 ± 0.2 g/L under all three O2 concentrations. However, poly-(R)-3-hydroxybutyrate content was 71, 77 and 58% of the cell dry weight with 1, 2 and 4% dissolved O2, respectively.
Microbial Ecology of Pecorino Siciliano PDO Cheese Production Systems
Authors: Ruta Silvia , Murray Matthew , Kampff Zoe , McDonnell Brian , Lugli Gabriele Andrea , Ventura Marco , Todaro Massimo , Settanni Luca , van Sinderen Douwe , Mahony Jennifer
Published: June 2023

Pecorino Siciliano PDO is a semi-hard cheese that is produced in wooden vats using raw sheep’s milk and its associated autochthonous microbial community. In the present study, we evaluated the microbial ecology of the milk, curd and whey from five Pecorino Siciliano PDO-producing farms in Sicily using a combination of metagenomic and microbiological approaches. We present an overview of the species and strain-level diversity of dairy lactococcal and streptococcal isolates using established genotyping tools and compare the lactic acid bacterial populations present in samples from these farms. Whole genome sequences of representative isolates of Lactococcus spp. and Streptococcus thermophilus were elucidated and the genetic diversity of the strains was established through analysis of predicted phage-resistance systems and prophage-associated regions. The analysis revealed farm-specific dairy lactococcal and streptococcal isolates that possess diverse genotypic features including newly described phage-resistance systems.
Intelligent Identification Method of Geographic Origin for Chinese Wolfberries Based on Color Space Transformation and Texture Morphological Features
Authors: He Jiawang , Wang Tianshu , Yan Hui , Guo Sheng , Hu Kongfa , Yang Xichen , Ma Chenlu , Duan Jinao
Published: June 2023

Geographic origins play a vital role in traditional Chinese medicinal materials. Using the geo-authentic crude drug can improve the curative effect. The main producing areas of Chinese wolfberry are Ningxia, Gansu, Qinghai, and so on. The geographic origin of Chinese wolfberry can affect its texture, shape, color, smell, nutrients, etc. However, the traditional method for identifying the geographic origin of Chinese wolfberries is still based on human eyes. To efficiently identify Chinese wolfberries from different origins, this paper presents an intelligent identification method for Chinese wolfberries based on color space transformation and texture morphological features. The first step is to prepare the Chinese wolfberry samples and collect the image data. Then the images are preprocessed, and the texture and morphology features of single wolfberry images are extracted. Finally, the random forest algorithm is employed to establish a model of the geographic origin of Chinese wolfberries. The proposed method can accurately predict the origin information of a single wolfberry image and has the advantages of low cost, fast recognition speed, high recognition accuracy, and no damage to the sample.
Fabrication and Characterization of Novel Food-Grade Bigels Based on Interfacial and Bulk Stabilization
Authors: Li Jiaxi , Han Junze , Xiao Yahao , Guo Ruihua , Liu Xinke , Zhang Hong , Bi Yanlan , Xu Xuebing
Published: June 2023

Novel food-grade bigels were fabricated using zein nanoparticles for interfacial stabilization and non-surfactant gelators (beeswax and tapioca) for bulk stabilization. The present study demonstrated the importance of interfacial stability for biphasic gels and sheds light on the roles of the gelation mechanism and the oil/water ratio of a bigel on its microstructure, physical properties, and digestion behaviors. The results indicated that it is not an easy task to realize homogenization and subsequent gelation in beeswax–tapioca biphasic systems, as no amphiphilic components existed. However, applying the binding of zein nanoparticles at the oil–water interface allowed us to produce a homogeneous and stable bigel (oil fraction reach 40%), which exhibited enhanced structural and functional properties. Oleogel structures play a crucial role in determining the deformation response of bigel systems. As the oil content increased, the mechanical strength and elastic properties of bigels were enhanced. In the meantime, clear bigel-type transitions were observed. In addition, the fabricated bigels were shown to be beneficial for delayed digestion, and the lowest degree of lipolysis could be found in bigel with 50% oleogel.
Patterns of Third-Molar-Pericoronitis-Related Pain: A Morphometrical Observational Retrospective Study
Authors: Chisci Dafne , Parrini Stefano , Baldini Nicola , Chisci Glauco
Published: June 2023

Background: Mandibular third molar (M3M) removal and the management of postoperative complications represent a common matter of interest in oral and maxillofacial surgery. Pain represents a great symptom for patients affected by pericoronitis and it is the most common indication for third molar removal. The aim of the present article is to search for patterns of pre-operative pain in patients before undergoing third molar surgery and to test for a relation between some patterns of symptoms, such as pain intensity, site of symptomatic tooth, and referred area of pain. Methods: This retrospective observational study enrolled a total of 86 patients, aged (mean ± SD) 34.54 ± 13.62 years (range 17–78 years), scheduled for outpatient third molar extraction at the Oral Surgery School, Department of Medical Biotechnologies, Policlinico “Le Scotte”, University of Siena. Pericoronitis and pain were the symptoms of the patients and the indication of extraction. Inclusion criteria were the presence of partially impacted third molars, confirmed with a preoperative panoramic radiograph, and preoperative pain. Exclusion criteria were known neurological disease (such as previous trigeminal or facial nerve injuries), impaired communicative or cognitive disease, diagnosed diabetes mellitus, and oral surgical intervention within 30 days before data collection. Patients were visited and asked to answer a morphometric analytic questionnaire about their perception of pain referred to the third molar. Analyses were performed on statistical evaluation on age, age ranges, patient gender, prior third molar extraction, site of pericoronitis, pain score (1–10), and pain area. Two-tailed p values of less than 0.05 were considered significant if not otherwise specified. Results: No correlations were found between age, gender, previous extraction, tooth site (maxillar on mandible), pain score, and pain area. Patterns of third molar pericoronitis pain among 86 patients were reported. A significant correlation was found between pain score and pain area (p = 0.0111, rs = 0.3131). Conclusions: Pain intensity has indeed some kind of responsibility in determining the orofacial distribution of pain. The pain area referral patterns of the present article could be considered as a pain model resulting from the pericoronitis of maxillar and mandibular third molars.
A Systematic Review of Clinical Practice Guidelines for Caries Prevention following the AGREE II Checklist
Authors: Lamloum Demetrio , Arghittu Antonella , Ferrara Pietro , Castiglia Paolo , Dettori Marco , Gaeta Maddalena , Odone Anna , Campus Guglielmo
Published: June 2023

Untreated oral diseases are detrimental to overall well-being and quality of life and are in close relationship with social and economic consequences. The presence of strong evidence for caries primary and secondary prevention is a compulsory tool for the development of clinical practice guidelines (CPGs). This paper was aimed to assess systematically the importance of clinical practice guidelines in caries prevention management considering both the adult and pediatric populations and evaluate them using the Appraisal of Guidelines for Research and Evaluation (AGREE II) Checklist. Records were extracted from EMBASE, SCOPUS, PubMed/Medline and seven other relevant guideline databases between 6 January and 14 February 2023. Two reviewers independently conducted the appraisal using the web-based platform My AGREE PLUS. Twenty-one guidelines/papers met the inclusion criteria and were reviewed. Eight CPGs included both primary and secondary prevention interventions, whereas thirteen presented a single preventive model. Overall, 12 guidelines were published in the USA. The mean AGREE II scores ranged from 35.4% to 84.3%. Of the total twenty-one included guidelines, twelve were classified as “Recommended”, ranging from 56.3% to 84.3%, the others were described as “Recommended with modification”, ranging from 35.4% to 68.9%. From the AGREE II analysis carried out, the CPGs included in this survey adopted a punctual methodological rigor but lacked applicative power. The present survey showed that the public, as the primary beneficiary, played a limited role in the development of the twenty-one CPGs. Hence, methodological improvement can better support high-quality CPG development in the future.
A Proxy Approach to Family Involvement and Neurocognitive Function in First Episode of Non-Affective Psychosis: Sex-Related Differences
Authors: Soler-Andrés Marina , Díaz-Pons Alexandre , Ortiz-García de la Foz Víctor , Murillo-García Nancy , Barrio-Martínez Sara , Miguel-Corredera Margarita , Yorca-Ruiz Angel , Magdaleno Herrero Rebeca , Moya-Higueras Jorge , Setién-Suero Esther , Ayesa-Arriola Rosa
Published: June 2023

Schizophrenia spectrum disorders (SSD) often show cognitive deficits (CD) impacting daily life. Family support has been shown to be protective against CD, yet the relationship between these in psychotic patients remains complex and not fully understood. This study investigated the association between a subdomain of family support, namely, family involvement (estimated through a proxy measure), cognitive functioning, and sex in first-episode psychosis (FEP) patients. The sample included 308 patients enrolled in the Program for Early Phases of Psychosis (PAFIP), divided into 4 groups based on their estimated family involvement (eFI) level and sex, and compared on various variables. Women presented lower rates of eFI than men (37.1% and 48.8%). Higher eFI was associated with better cognitive functioning, particularly in verbal memory. This association was stronger in women. The findings suggest that eFI may be an important factor in FEP patients’ cognitive functioning. This highlights the importance of including families in treatment plans for psychotic patients to prevent CD. Further research is needed to better understand the complex interplay between family support, sex, and cognitive functioning in psychotic patients and develop effective interventions that target these factors.
The Challenges of Gastric Cancer Surgery during the COVID-19 Pandemic
Authors: Feier Catalin Vladut Ionut , Faur Alaviana Monique , Muntean Calin , Blidari Andiana , Contes Oana Elena , Streinu Diana Raluca , Olariu Sorin
Published: June 2023

The aim of this study was to quantify the impact of the COVID-19 pandemic on the surgical treatment of patients with gastric cancer. Data from patients undergoing surgery for gastric cancer during the pandemic were analyzed and the results obtained were compared with the corresponding periods of 2016–2017 and 2018–2019. Various parameters were taken into consideration and their dynamics highlight significant changes in the pandemic year compared with the two pre-pandemic periods. Statistical analysis revealed a marked decrease in the number of surgeries performed during the pandemic (p < 0.001). Severe prognostic factors for gastric cancer, including weight loss and upper gastrointestinal hemorrhage, were associated with an increased number of postoperative fistulas, while emesis was statistically correlated with a more advanced cancer stage (p < 0.011). There was also a reduction in the total duration of hospitalization (p = 0.044) and postoperative hospitalization (p = 0.047); moreover, the mean duration of surgical intervention was higher during the pandemic (p = 0.044). These findings provide evidence for the significant changes in clinical and therapeutic strategies applied to patients undergoing surgery for gastric cancer during the study period. The ongoing pandemic has exerted a substantial and complex impact, the full extent of which remains yet to be fully comprehended.
Genome-Wide Resequencing Reveals Genetic Relationships between Main Gardenia jasminoides Ellis Cultivars
Authors: Li Kangqin , Gao Liqin , Yang Xiaoli , Wang Meixia , Feng Xiaotao , Deng Shaoyong
Published: June 2023

Nineteen samples of Gardenia jasminoides Ellis from China were used for genome resequencing. The clean Q30 base rates ranged from 91.19% to 92.94%. When mapping with the reference genome, a total of 7,568,199 inDel sites and 61,535,595 SNP sites were detected, with variations of heterozygosity ratios ranging from 44.86% to 92.69% and from 41.53% to 90.38%, respectively. Genome location and function annotation of SNP and inDel in different samples were carried out. SNP and inDel were mainly located in the intergenic region, with the ratios of 67.2360% and 62.6415%, respectively. Based on the phylogenetic tree constructed by the maximum likelihood method, the 19 samples could be divided into four categories. Among them, Y_10 and Y_38 were put into one category, while Y_2 was put into a separate category. These two were first differentiated from other cultivars and species. Similar conclusions can be drawn from the results of genetic structure and principal component analysis. This study provided sequence foundation for the identifying of the molecular marker and genotype of G. jasminoides. It also provided theoretical foundation for subsequent resource conservation and utilization, the genetic localization of important agronomical traits, and high-quality variety formulation and breeding.
Effects of a Gravel Pit Lake on Groundwater Hydrodynamic
Authors: Vrzel Janja , Kupfersberger Hans , Rivera Villarreyes Carlos Andres , Fank Johann , Wieser Leander
Published: June 2023

In Europe, 1132 Mt of sand and gravel were mined in 2019, which causes major changes to the hydrogeological cycle. Such changes may lead to significantly raised or lowered groundwater levels. Therefore, the aggregate sector has to ensure that impacts on existing environmental and water infrastructures are kept to a minimum in the post-mining phase. Such risk assessments are often made by empirical methods, which are based on assumptions that do not meet real aquifer conditions. To investigate this effect, predictions by empirical and numerical methods about hydraulic head changes caused by a pit lake were compared. Wrobel’s equation, which is based on Sichardt’s equation, was used as the empirical method, while a numerical groundwater flow model has been solved by means of the finite-element method in FEFLOW. The empirical method provides significantly smaller ranges of increased/decreased groundwater levels caused by the gravel pit lake as the numerical method. The underestimation of the empirical results was related to the finding that field measurements during pumping tests show a larger extent of groundwater drawdown than calculations with the Sichardt’s equation. Simplifications of the 2D model approach have been evaluated against hydraulic head changes derived from a 3D groundwater model. Our results clearly show that the faster and cheaper empirical method—Wrobel’s equation, which is often preferred over the more expensive and time-consuming numerical method, underestimates the drawdown area. This is especially critical when the assignment of mining permits is based on such computations. Therefore, we recommend using numerical models in the pre-mining phase to accurately compute the extent of a gravel/sand excavation’s impacts on hydraulic head and hence more effective protection of groundwater and other related environmental systems.
Comprehensive Overview of Flood Modeling Approaches: A Review of Recent Advances
Authors: Kumar Vijendra , Sharma Kul , Caloiero Tommaso , Mehta Darshan , Singh Karan
Published: June 2023

As one of nature’s most destructive calamities, floods cause fatalities, property destruction, and infrastructure damage, affecting millions of people worldwide. Due to its ability to accurately anticipate and successfully mitigate the effects of floods, flood modeling is an important approach in flood control. This study provides a thorough summary of flood modeling’s current condition, problems, and probable future directions. The study of flood modeling includes models based on hydrologic, hydraulic, numerical, rainfall–runoff, remote sensing and GIS, artificial intelligence and machine learning, and multiple-criteria decision analysis. Additionally, it covers the heuristic and metaheuristic techniques employed in flood control. The evaluation examines the advantages and disadvantages of various models, and evaluates how well they are able to predict the course and impacts of floods. The constraints of the data, the unpredictable nature of the model, and the complexity of the model are some of the difficulties that flood modeling must overcome. In the study’s conclusion, prospects for development and advancement in the field of flood modeling are discussed, including the use of advanced technologies and integrated models. To improve flood risk management and lessen the effects of floods on society, the report emphasizes the necessity for ongoing research in flood modeling.
Pathophysiological and Molecular Basis of the Side Effects of Ticagrelor: Lessons from a Case Report
Authors: Cesarini Daniel , Muraca Iacopo , Berteotti Martina , Gori Anna Maria , Sorrentino Andrea , Bertelli Alessia , Marcucci Rossella , Valenti Renato
Published: June 2023

Ticagrelor is currently considered a first-line choice in dual antiplatelet therapy (DAPT) following revascularization of acute coronary syndrome (ACS). However, its use is correlated with an increased incidence of two side effects, dyspnea and bradyarrhythmias, whose molecular mechanisms have not yet been defined with certainty and, consequently, neither of the therapeutic decisions they imply. We report the case of a patient with acute myocardial infarction treated with ticagrelor and aspirin as oral antithrombotic therapy after primary percutaneous coronary intervention (PCI), manifesting in a significant bradyarrhythmic episode that required a switch of antiplatelet therapy. Starting from this case report, this article aims to gather the currently available evidence regarding the molecular mechanisms underlying these side effects and propose possible decision-making algorithms regarding their management in clinical practice.
Relevance of KCNJ5 in Pathologies of Heart Disease
Authors: Meyer Karisa M. , Malhotra Nipun , Kwak Jung seo , El Refaey Mona
Published: June 2023

Abnormalities in G-protein-gated inwardly rectifying potassium (GIRK) channels have been implicated in diseased states of the cardiovascular system; however, the role of GIRK4 (Kir3.4) in cardiac physiology and pathophysiology has yet to be completely understood. Within the heart, the KACh channel, consisting of two GIRK1 and two GIRK4 subunits, plays a major role in modulating the parasympathetic nervous system’s influence on cardiac physiology. Being that GIRK4 is necessary for the functional KACh channel, KCNJ5, which encodes GIRK4, it presents as a therapeutic target for cardiovascular pathology. Human variants in KCNJ5 have been identified in familial hyperaldosteronism type III, long QT syndrome, atrial fibrillation, and sinus node dysfunction. Here, we explore the relevance of KCNJ5 in each of these diseases. Further, we address the limitations and complexities of discerning the role of KCNJ5 in cardiovascular pathophysiology, as identical human variants of KCNJ5 have been identified in several diseases with overlapping pathophysiology.
Comparative Transcriptome Analysis Reveals Novel Candidate Resistance Genes Involved in Defence against Phytophthora cactorum in Strawberry
Authors: Gogoi Anupam , Lysøe Erik , Eikemo Håvard , Stensvand Arne , Davik Jahn , Brurberg May Bente
Published: June 2023

Crown rot, caused by Phytophthora cactorum, is a devastating disease of strawberry. While most commercial octoploid strawberry cultivars (Fragaria × ananassa Duch) are generally susceptible, the diploid species Fragaria vesca is a potential source of resistance genes to P. cactorum. We previously reported several F. vesca genotypes with varying degrees of resistance to P. cactorum. To gain insights into the strawberry defence mechanisms, comparative transcriptome profiles of two resistant genotypes (NCGR1603 and Bukammen) and a susceptible genotype (NCGR1218) of F. vesca were analysed by RNA-Seq after wounding and subsequent inoculation with P. cactorum. Differential gene expression analysis identified several defence-related genes that are highly expressed in the resistant genotypes relative to the susceptible genotype in response to P. cactorum after wounding. These included putative disease resistance (R) genes encoding receptor-like proteins, receptor-like kinases, nucleotide-binding sites, leucine-rich repeat proteins, RPW8-type disease resistance proteins, and ‘pathogenesis-related protein 1’. Seven of these R-genes were expressed only in the resistant genotypes and not in the susceptible genotype, and these appeared to be present only in the genomes of the resistant genotypes, as confirmed by PCR analysis. We previously reported a single major gene locus RPc-1 (Resistance to Phytophthora cactorum 1) in F. vesca that contributed resistance to P. cactorum. Here, we report that 4–5% of the genes (35–38 of ca 800 genes) in the RPc-1 locus are differentially expressed in the resistant genotypes compared to the susceptible genotype after inoculation with P. cactorum. In particular, we identified three defence-related genes encoding wall-associated receptor-like kinase 3, receptor-like protein 12, and non-specific lipid-transfer protein 1-like that were highly expressed in the resistant genotypes compared to the susceptible one. The present study reports several novel candidate disease resistance genes that warrant further investigation for their role in plant defence against P. cactorum.
Phytoestrogens Present in Follicular Fluid and Urine Are Positively Associated with IVF Outcomes following Single Euploid Embryo Transfer
Authors: Gonzalez-Martin Roberto , Palomar Andrea , Quiñonero Alicia , Pellicer Nuria , Zuckerman Caroline , Whitehead Christine , Scott Richard T. , Dominguez Francisco
Published: June 2023

The impact and safety of phytoestrogens, plant-derived isoflavones with estrogenic activity predominantly present in soy, on female reproductive health and IVF outcomes continues to be hotly debated. In this prospective cohort study, 60 women attending IVI-RMA New Jersey undergoing IVF with single frozen embryo transfer (SET/FET) of good-quality euploid blastocyst after PGT-A analysis were recruited. Concentrations of two phytoestrogens (daidzein and genistein) in follicular fluid (FF) and urine (U) were measured by UPLC–MSMS, both collected on vaginal oocyte retrieval day. These measurements correlated with IVF clinical outcomes. In models adjusted for age, BMI, race/ethnicity, and smoking status, higher FF phytoestrogen concentrations were significantly associated with higher serum estradiol, enhanced probability of implantation, clinical pregnancy, and live birth. Moreover, higher urine phytoestrogen concentrations were significantly associated with improved oocyte maturation and fertilization potential and increased probability of clinical pregnancy and live birth. Finally, higher FF and urine phytoestrogen concentrations were associated with a higher probability of live birth from a given IVF cycle. Our results suggest that dietary phytoestrogens improved reproductive outcomes of women undergoing IVF treatment. However, additional prospective studies are needed to optimize the use of phytoestrogens to further enhance reproductive outcomes and/or protect against reproductive insults.
Using the Random Forest for Identifying Key Physicochemical Properties of Amino Acids to Discriminate Anticancer and Non-Anticancer Peptides
Authors: Deng Yiting , Ma Shuhan , Li Jiayu , Zheng Bowen , Lv Zhibin
Published: June 2023

Anticancer peptides (ACPs) represent a promising new therapeutic approach in cancer treatment. They can target cancer cells without affecting healthy tissues or altering normal physiological functions. Machine learning algorithms have increasingly been utilized for predicting peptide sequences with potential ACP effects. This study analyzed four benchmark datasets based on a well-established random forest (RF) algorithm. The peptide sequences were converted into 566 physicochemical features extracted from the amino acid index (AAindex) library, which were then subjected to feature selection using four methods: light gradient-boosting machine (LGBM), analysis of variance (ANOVA), chi-squared test (Chi2), and mutual information (MI). Presenting and merging the identified features using Venn diagrams, 19 key amino acid physicochemical properties were identified that can be used to predict the likelihood of a peptide sequence functioning as an ACP. The results were quantified by performance evaluation metrics to determine the accuracy of predictions. This study aims to enhance the efficiency of designing peptide sequences for cancer treatment.
Mesenchymal Stem Cell Conditioned Medium Modulates Inflammation in Tenocytes: Complete Conditioned Medium Has Superior Therapeutic Efficacy than Its Extracellular Vesicle Fraction
Authors: Soukup Robert , Gerner Iris , Mohr Thomas , Gueltekin Sinan , Grillari Johannes , Jenner Florien
Published: June 2023

Tendinopathy, a prevalent overuse injury, lacks effective treatment options, leading to a significant impact on quality of life and socioeconomic burden. Mesenchymal stem/stromal cells (MSCs) and their secretome, including conditioned medium (CM) and extracellular vesicles (EVs), have shown promise in tissue regeneration and immunomodulation. However, it remains unclear which components of the secretome contribute to their therapeutic effects. This study aimed to compare the efficacy of CM, EVs, and the soluble protein fraction (PF) in treating inflamed tenocytes. CM exhibited the highest protein and particle concentrations, followed by PF and EVs. Inflammation significantly altered gene expression in tenocytes, with CM showing the most distinct separation from the inflamed control group. Treatment with CM resulted in the most significant differential gene expression, with both upregulated and downregulated genes related to inflammation and tissue regeneration. EV treatment also demonstrated a therapeutic effect, albeit to a lesser extent. These findings suggest that CM holds superior therapeutic efficacy compared with its EV fraction alone, emphasizing the importance of the complete secretome in tendon injury treatment.
Structurally and Morphologically Distinct Pathological Tau Assemblies Differentially Affect GVB Accumulation
Authors: Jorge-Oliva Marta , van Weering Jan R. T. , Scheper Wiep
Published: June 2023

Tau aggregation is central to the pathogenesis of a large group of neurodegenerative diseases termed tauopathies, but it is still unclear in which way neurons respond to tau pathology and how tau accumulation leads to neurodegeneration. A striking neuron-specific response to tau pathology is presented by granulovacuolar degeneration bodies (GVBs), lysosomal structures that accumulate specific cargo in a dense core. Here we employed different tau aggregation models in primary neurons to investigate which properties of pathological tau assemblies affect GVB accumulation using a combination of confocal microscopy, transmission electron microscopy, and quantitative automated high-content microscopy. Employing GFP-tagged and untagged tau variants that spontaneously form intraneuronal aggregates, we induced pathological tau assemblies with a distinct subcellular localization, morphology, and ultrastructure depending on the presence or absence of the GFP tag. The quantification of the GVB load in the different models showed that an increased GVB accumulation is associated with the untagged tau aggregation model, characterized by shorter and more randomly distributed tau filaments in the neuronal soma. Our data indicate that tau aggregate structure and/or subcellular localization may be key determinants of GVB accumulation.
CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy
Authors: Wang Yizheng , Wang Linan , Seo Naohiro , Okumura Satoshi , Hayashi Tae , Akahori Yasushi , Fujiwara Hiroshi , Amaishi Yasunori , Okamoto Sachiko , Mineno Junichi , Tanaka Yoshimasa , Kato Takuma , Shiku Hiroshi
Published: June 2023

The benefits of CAR-T therapy could be expanded to the treatment of solid tumors through the use of derived autologous αβ T cell, but clinical trials of CAR-T therapy for patients with solid tumors have so far been disappointing. CAR-T therapy also faces hurdles due to the time and cost intensive preparation of CAR-T cell products derived from patients as such CAR-T cells are often poor in quality and low in quantity. These inadequacies may be mitigated through the use of third-party donor derived CAR-T cell products which have a potent anti-tumor function but a constrained GVHD property. Vγ9Vδ2 TCR have been shown to exhibit potent antitumor activity but not alloreactivity. Therefore, in this study, CAR-T cells were prepared from Vγ9Vδ2 T (CAR-γδ T) cells which were expanded by using a novel prodrug PTA. CAR-γδ T cells suppressed tumor growth in an antigen specific manner but only during a limited time window. Provision of GITR co-stimulation enhanced anti-tumor function of CAR-γδ T cells. Our present results indicate that, while further optimization of CAR-γδ T cells is necessary, the present results demonstrate that Vγ9Vδ2 T cells are potential source of ‘off-the-shelf’ CAR-T cell products for successful allogeneic adoptive immunotherapy.
Infection, Dysbiosis and Inflammation Interplay in the COVID Era in Children
Authors: Ailioaie Laura Marinela , Ailioaie Constantin , Litscher Gerhard
Published: June 2023

For over three years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents has generated repercussions, especially a few weeks after infection, for symptomatic patients who tested positive, for asymptomatic ones, or even just the contacts of an infected person, and evolved from severe forms such as multisystem inflammatory syndrome in children (MIS-C) to multifarious clinical manifestations in long COVID (LC). Referred to under the umbrella term LC, the onset of persistent and highly heterogeneous symptoms such as fatigue, post-exertion malaise, cognitive dysfunction, and others have a major impact on the child’s daily quality of life for months. The first aim of this review was to highlight the circumstances of the pathophysiological changes produced by COVID-19 in children and to better understand the hyperinflammation in COVID-19 and how MIS-C, as a life-threatening condition, could have been avoided in some patients. Another goal was to better identify the interplay between infection, dysbiosis, and inflammation at a molecular and cellular level, to better guide scientists, physicians, and pediatricians to advance new lines of medical action to avoid the post-acute sequelae of SARS-CoV-2 infection. The third objective was to identify symptoms and their connection to molecular pathways to recognize LC more easily. The fourth purpose was to connect the triggering factors of LC with related sequelae following acute SARS-CoV-2 injuries to systems and organs, the persistence of the virus, and some of its components in hidden reservoirs, including the gut and the central nervous system. The reactivation of other latent infectious agents in the host’s immune environments, the interaction of this virus with the microbiome, immune hyperactivation, and autoimmunity generated by molecular mimicry between viral agents and host proteins, could initiate a targeted and individualized management. New high-tech solutions, molecules, probiotics, and others should be discovered to innovatively solve the interplay between RNA persistent viruses, microbiota, and our immune system.
Visceral Obesity and Cytokeratin-18 Antigens as Early Biomarkers of Liver Damage
Authors: de Alteriis Giulia , Pugliese Gabriella , Di Sarno Antonella , Muscogiuri Giovanna , Barrea Luigi , Cossiga Valentina , Perruolo Giuseppe , Di Tolla Michele Francesco , Zumbolo Francesca , Formisano Pietro , Morisco Filomena , Savastano Silvia
Published: June 2023

Visceral obesity is linked to the progression of fatty liver to nonalcoholic steatohepatitis (NASH). Cytokeratin-18 (CK18) epitopes M30 (CK18M30) and M65 (CK18M65) represent accurate markers for detecting NASH. The aim of this study was to evaluate the association of CK18M30 and CK18M65 levels with anthropometric and metabolic characteristics, liver stiffness, and liver indices of steatosis and fibrosis in a cohort of subjects with visceral obesity; in this cross-sectional study, transient elastography (TE-Fibroscan®), anthropometric measurements, metabolic parameters, High Sensitivity C-Reactive Protein (hsCRP), and CK18M30 and CK18M65 levels (Apoptosense ELISA, PEVIVA, Germany) were evaluated. Fatty Liver Index (FLI), Fibrosis 4 (FIB-4), and Aspartate transaminase (AST)-platelet ratio index (APRI) were calculated; among 48 subjects, 47.2% presented metabolic syndrome, 93.8% hepatic steatosis, 60.4% high liver stiffness, and 14.6% hypertransminasemia, while FIB-4 and APRI were normal. CK18M30 and CK18M65 levels were significantly correlated with waist circumference, AST, ALT, HoMA-IR, liver stiffness, and APRI (p < 0.001). Subjects with CK18 fragments above the median values showed significantly higher waist circumference, HbA1c, AST, ALT, HoMA-IR, FLI, and APRI compared to those with values below the median; CK18M30 and CK18M65 levels correlated well with anthropometric and metabolic characteristics, representing good biomarkers for early identification of NASH in subjects with visceral obesity.
CRP in Outpatients with Inflammatory Bowel Disease Is Linked to the Blood Microbiota
Authors: Xu Jie , Molin Göran , Davidson Sanna , Roth Bodil , Sjöberg Klas , Håkansson Åsa
Published: June 2023

The circulation is a closed system that has been assumed to be free from bacteria, but evidence for the existence of a low-density blood microbiota is accumulating. The present study aimed to map the blood microbiota of outpatients with Crohn’s disease (CD) or with ulcerative colitis (UC) by 16S metagenomics. A diverse microbiota was observed in the blood samples. Regardless of the type of disease, the alpha diversity of the microbiota was positively associated with C-reactive protein (CRP). The blood microbiota had a surprisingly high proportion of Proteobacteria in comparison with human oral and colonic microbiotas. There was no clear difference in the overall pattern of the microbiota between CD and UC. A non-template control (NTC) was included in the whole process to control for the potential contamination from the environment and reagents. Certain bacterial taxa were concomitantly detected in both blood samples and NTC. However, Acinetobacter, Lactobacillus, Thermicanus and Paracoccus were found in blood from both CD and UC patients but not in NTC, indicating the existence of a specific blood-borne microbiota in the patients. Achromobacter dominated in all blood samples, but a minor amount was also found in NTC. Micrococcaceae was significantly enriched in CD, but it was also detected in high abundance in NTC. Whether the composition of the blood microbiota could be a marker of a particular phenotype in inflammatory bowel disease (IBD) or whether the blood microbiota could be used for diagnostic or therapeutic purposes deserves further attention.
Discovery and Mechanism of Novel 7-Aliphatic Amine Tryptanthrin Derivatives against Phytopathogenic Bacteria
Authors: Long Xuesha , Zhang Guanglong , Long Haitao , Wang Qin , Wang Congyu , Zhu Mei , Wang Wenhang , Li Chengpeng , Wang Zhenchao , Ouyang Guiping
Published: June 2023

Rice bacterial leaf blight is a destructive bacterial disease caused by Xanthomonas oryzae pv. oryzae (Xoo) that seriously threatens crop yields and their associated economic benefits. In this study, a series of improved dissolubility 7-aliphatic amine tryptanthrin derivatives was designed and synthesized, and their potency in antibacterial applications was investigated. Notably, compound 6e exhibited excellent activity against Xoo, with an EC50 value of 2.55 μg/mL, compared with the positive control bismerthiazol (EC50 = 35.0 μg/mL) and thiodiazole copper (EC50 = 79.4 μg/mL). In vivo assays demonstrated that 6e exhibited a significant protective effect on rice leaves. After exposure, the morphology of the bacteria was partially atrophied by SEM. Furthermore, 6e increased the accumulation of intracellular reactive oxygen species, causing cell apoptosis and the formation of bacterial biofilms. All the results indicated that 6e could be a potential agrochemical bactericide for controlling phytopathogenic bacteria.
Plants’ Response to Abiotic Stress: Mechanisms and Strategies
Authors: Zhang Yan , Xu Jing , Li Ruofan , Ge Yanrui , Li Yufei , Li Ruili
Published: June 2023

Abiotic stress is the adverse effect of any abiotic factor on a plant in a given environment, impacting plants’ growth and development. These stress factors, such as drought, salinity, and extreme temperatures, are often interrelated or in conjunction with each other. Plants have evolved mechanisms to sense these environmental challenges and make adjustments to their growth in order to survive and reproduce. In this review, we summarized recent studies on plant stress sensing and its regulatory mechanism, emphasizing signal transduction and regulation at multiple levels. Then we presented several strategies to improve plant growth under stress based on current progress. Finally, we discussed the implications of research on plant response to abiotic stresses for high-yielding crops and agricultural sustainability. Studying stress signaling and regulation is critical to understand abiotic stress responses in plants to generate stress-resistant crops and improve agricultural sustainability.
Mesenchymal Stem Cells and Exosomes: A Novel Therapeutic Approach for Corneal Diseases
Authors: Bhujel Basanta , Oh Se-Heon , Kim Chang-Min , Yoon Ye-Ji , Kim Young-Jae , Chung Ho-Seok , Ye Eun-Ah , Lee Hun , Kim Jae-Yong
Published: June 2023

The cornea, with its delicate structure, is vulnerable to damage from physical, chemical, and genetic factors. Corneal transplantation, including penetrating and lamellar keratoplasties, can restore the functions of the cornea in cases of severe damage. However, the process of corneal transplantation presents considerable obstacles, including a shortage of available donors, the risk of severe graft rejection, and potentially life-threatening complications. Over the past few decades, mesenchymal stem cell (MSC) therapy has become a novel alternative approach to corneal regeneration. Numerous studies have demonstrated the potential of MSCs to differentiate into different corneal cell types, such as keratocytes, epithelial cells, and endothelial cells. MSCs are considered a suitable candidate for corneal regeneration because of their promising therapeutic perspective and beneficial properties. MSCs compromise unique immunomodulation, anti-angiogenesis, and anti-inflammatory properties and secrete various growth factors, thus promoting corneal reconstruction. These effects in corneal engineering are mediated by MSCs differentiating into different lineages and paracrine action via exosomes. Early studies have proven the roles of MSC-derived exosomes in corneal regeneration by reducing inflammation, inhibiting neovascularization, and angiogenesis, and by promoting cell proliferation. This review highlights the contribution of MSCs and MSC-derived exosomes, their current usage status to overcome corneal disease, and their potential to restore different corneal layers as novel therapeutic agents. It also discusses feasible future possibilities, applications, challenges, and opportunities for future research in this field.
Glypican-3 (GPC-3) Structural Analysis and Cargo in Serum Small Extracellular Vesicles of Hepatocellular Carcinoma Patients
Authors: Mauro Montalbano , Ugo Perricone , Walton Zachary , Ali Shirafkan , Rastellini Cristiana , Cicalese Luca
Published: June 2023

Glypican-3 (GPC-3) is a heparin sulfate proteoglycan located extracellularly and anchored to the cell membrane of transformed hepatocytes. GPC-3 is not expressed in normal or cirrhotic liver tissue but is overexpressed in hepatocellular carcinoma (HCC). Because of this, GPC-3 is one of the most important emerging immunotargets for treatment and as an early detection marker of HCC. To determine if GPC-3 domains associated with serum small extracellular vesicles (sEVs) could be used as an HCC diagnostic marker, we predicted in silico GPC-3 structural properties and tested for the presence of its full-length form and/or cleaved domains in serum sEVs isolated from patients with HCC. Structural analysis revealed that the Furin cleavage site of GPC-3 is exposed and readily accessible, suggesting the facilitation of GPC-3 cleavage events. Upon isolation of sEVs from both hepatocytes, culture media and serum of patients with HCC were studied for GPC-3 content. This data suggests that Furin-dependent GPC-3 cleaved domains could be a powerful tool for detection of initial stages of HCC and serve as a predictor for disease prognosis.
Molecular Dynamics Study of the Effect of Charge and Glycosyl on Superoxide Anion Distribution near Lipid Membrane
Authors: Meng Xuan , Liu Huiyu , Zhao Ning , Yang Yajun , Zhao Kai , Dai Yujie
Published: June 2023

To examine the effects of membrane charge, the electrolyte species and glycosyl on the distribution of negatively charged radical of superoxide anion (·O2−) around the cell membrane, different phospholipid bilayer systems containing ·O2− radicals, different electrolytes and phospholipid bilayers were constructed through Charmm-GUI and Amber16. These systems were equilibrated with molecular dynamics by using Gromacs 5.0.2 to analyze the statistical behaviors of ·O2− near the lipid membrane under different conditions. It was found that in the presence of potassium rather than sodium, the negative charge of the phospholipid membrane is more likely to rarefy the superoxide anion distribution near the membrane surface. Further, the presence of glycosyl significantly reduced the density of ·O2− near the phospholipid bilayer by 78.3% compared with that of the neutral lipid membrane, which may have a significant contribution to reducing the lipid peroxidation from decreasing the ·O2− density near the membrane.