bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Review of the Role of Multimodal Resources for Inclusive STEM Engagement in Early-Childhood Education
Authors: Kewalramani Sarika , Aranda George , Sun Jiqing , Richards Gerarda , Hobbs Linda , Xu Lihua , Millar Victoria , Dealy Belinda , Van Leuven Bridgette
Published: June 2024

This paper presents the findings from a systematic review of 29 websites and 13 frameworks that provide STEM (Science, Technology, Engineering, Mathematics) educational resources for parents, educators, and children (birth–8 years of age). Our theoretical approach is rooted within a social semiotic perspective that has indicated that multimodality enables children to use different types of expression to communicate a message or share an idea. Using the PRISMA methodology and the narrative document analysis approach, the themes that emerged included how the content and resources available on the websites addressed whether multimodality supported STEM engagement in an inclusive manner. The findings revealed that there were scarce multimodal resources that engaged children with fun, interactive, and meaningful opportunities to be autonomous learners (e.g., children had agency) (n = 11 out of 29), moving between the digital and hands-on physical spaces (n = 8 out of 29), employing gamification for deep learning (n = 4 out of 29), and piquing children’s imagination, inquiry, and creativity, and links to everyday STEM scenarios were hardly present (n = 10 out of 29). The implications lie in addressing early STEM engagement by considering children’s learning abilities and agency, bearing in mind parents/educators’ sociocultural backgrounds, confidence in STEM awareness, and multimodal avenues for communicating STEM learning and inquiry.
Instructional Videos for Students in Dental Medicine: Rules of Design and Correlations with Their Habits as Internet Consumers
Authors: Dascalu Cristina Gena , Topoliceanu Claudiu , Antohe Magda Ecaterina
Published: June 2024

Multimedia resources, such as instructional videos, are currently enjoying a certain popularity in the training programs for medical and dental students. The major challenge is to create such resources with quality content that is approved by students. In order to answer this challenge, it is imperative to find out which features of instructional videos are considered to be necessary and useful by students, thus being able to excite them, to hold their attention, and to stimulate them in learning with pleasure. Aim: We investigated the opinions of a sample of 551 students from four medical universities in Romania, in order to identify the students’ preferred characteristics in instructional videos, both globally and comparatively on genders and age groups and also according to their general preferences for using internet services. Material and methods: We used univariate (hypothesis testing) and multivariate (two-step clustering) data analysis techniques and revealed three clusters of students, primarily determined by their perceptions of the visual appearance of the instructional videos. Results: The structure of the clusters by gender and age group was relatively similar, but we recorded differences associated with the students’ expressed preferences for certain internet services compared to others. The first identified cluster (35.4% of the cases) contains students who prefer instructional videos to contain images used only for aesthetic purposes and to fill the gaps; they use internet services mainly for communication. The second cluster of students (34.8%) prefers videos designed as practical lessons, using explanatory drawings and diagrams drawn at the same time as the explanations; they also use internet services mainly for communication. The last cluster of students (29.8%) prefer videos designed as PowerPoint presentations, with animated pictures, diagrams, and drawings; they are slightly younger than the others and use internet services mainly for information and communication, but also for domestic facilities. Conclusions: The students’ preferences for certain features of instructional videos depend not only on gender and age but are also related to their developmental background and general opinions about modern technologies.
Social Media News Headlines and Their Influence on Well-Being: Emotional States, Emotion Regulation, and Resilience
Authors: Mousoulidou Marilena , Taxitari Loukia , Christodoulou Andri
Published: June 2024

Today, many individuals read the daily news from social media platforms. Research has shown that news with negative valence might influence the well-being of individuals. Existing research that examined the impact of headlines on individuals’ well-being has primarily focused on examining the positive or negative polarity of words used in the headlines. In the present study, we adopt a different approach and ask participants to categorize the headlines themselves based on the emotions they experienced while reading them and how their choice impacts their well-being. A total of 306 participants were presented with 40 headlines from main news sites that were considered popular based on the number of public reactions. Participants had to rate their emotional experience of the headlines following five emotional states (i.e., happiness, anger, sadness, fear, and interest). Emotion regulation strategies and resilience were also measured. In line with our hypotheses, we found that participants reported experiencing negative emotions more intensively while reading the headlines. Emotion regulation was not found to influence the emotional states of individuals, whereas resilience did. These findings highlight that individuals can experience heightened emotions without reading the entire news story. This effect was observed regardless of the headline’s emotional valence (i.e., positive, negative, or neutral). Furthermore, our study highlights the critical role of interest as a factor in news consumption. Interest significantly affects individuals’ engagement and reactions to headlines, regardless of valence. The findings underscore the complex interplay between headline content and reader engagement and stress the need for further research into how headlines are presented to protect individuals from potential emotional costs.
Combined Light and Data Driving Stages without Capacitors for Energy Transformation
Authors: Windisch Michael , Himmelstoss Felix A. , Leba Monica , Stoicuta Olimpiu , Votzi Helmut L.
Published: June 2024

Three LED drivers which can be used for illumination, but whose main task is the transmission of information (data) via the light of the LEDs, are explored in this paper. The converter circuits need no capacitors for the energy transformation and avoid an inrush current. The lack of necessity of electrolytic capacitors reduces cost and space. Dimming the illumination is also easy to achieve. The control concept of the converters and the generation of pulsing of the LEDs for transmitting the information (data) are explained. The converters can also be expanded to more stages to drive more LEDs with different types of information. All three converters are explained in detail; all presented circuits are built up and simulated with LTSpice. Several data transmission concepts are applied and demonstrated through simulations.
High C-Rate Performant Electrospun LiFePO4/Carbon Nanofiber Self-Standing Cathodes for Lithium-Ion Batteries
Authors: Conti Debora Maria , Urru Claudia , Bruni Giovanna , Galinetto Pietro , Albini Benedetta , Berbenni Vittorio , Capsoni Doretta
Published: June 2024

In the present study, LiFePO4/CNF self-standing cathodes for LIBs are synthesized by electrospinning. A lower active material amount (12.3 and 34.5 wt%) is used, compared to the conventional tape-casted cathodes (70–85 wt%). The characterization techniques (XRPD, SEM, TEM, EDS, Raman spectroscopy, and thermogravimetry) confirm that the olivine-type structure of LiFePO4 is maintained in the binder-free electrodes, and the active material is homogeneously dispersed into and within the carbon nanofibers. The electrochemical investigation demonstrates that higher Li+ diffusion coefficients (1.36 × 10−11 cm2/s) and improved reversibility are reached for free-standing electrodes, compared to the LiFePO4 tape-casted cathode (80 wt% of active material) appositely prepared for comparison. The 34.5 wt% LiFePO4 self-standing cathode displays a lower capacity fading, good reversibility and stability, enhanced capacity values at C-rates higher than 5C, and a good lifespan when cycled 1000 cycles at 1C and further cycled up to 20C, compared to the tape-casted counterpart. Notably, the improved electrochemical performances are obtained by only the 34.5 wt% of active material. The results evidence the relevant role of the CNF matrix suitable to host LiFePO4, to promote electrolyte permeation and contact with the active material, and to increase the electronic conductivity.
Whole-Genome Sequence Analysis of Antibiotic Resistance, Virulence, and Plasmid Dynamics in Multidrug-Resistant E. coli Isolates from Imported Shrimp
Authors: Sung Kidon , Nawaz Mohamed , Park Miseon , Chon Jungwhan , Khan Saeed A. , Alotaibi Khulud , Revollo Javier , Miranda Jaime A. , Khan Ashraf A.
Published: June 2024

We analyzed antimicrobial resistance and virulence traits in multidrug-resistant (MDR) E. coli isolates obtained from imported shrimp using whole-genome sequences (WGSs). Antibiotic resistance profiles were determined phenotypically. WGSs identified key characteristics, including their multilocus sequence type (MLST), serotype, virulence factors, antibiotic resistance genes, and mobile elements. Most of the isolates exhibited resistance to gentamicin, streptomycin, ampicillin, chloramphenicol, nalidixic acid, ciprofloxacin, tetracycline, and trimethoprim/sulfamethoxazole. Multilocus sequence type (MLST), serotype, average nucleotide identity (ANI), and pangenome analysis showed high genomic similarity among isolates, except for EC15 and ECV01. The EC119 plasmid contained a variety of efflux pump genes, including those encoding the acid resistance transcriptional activators (gadE, gadW, and gadX), resistance-nodulation-division-type efflux pumps (mdtE and mdtF), and a metabolite, H1 symporter (MHS) family major facilitator superfamily transporter (MNZ41_23075). Virulence genes displayed diversity, particularly EC15, whose plasmids carried genes for adherence (faeA and faeC-I), invasion (ipaH and virB), and capsule (caf1A and caf1M). This comprehensive analysis illuminates antimicrobial resistance, virulence, and plasmid dynamics in E. coli from imported shrimp and has profound implications for public health, emphasizing the need for continued surveillance and research into the evolution of these important bacterial pathogens.
Quality- and Health-Promoting Compounds of Whole Wheat Bread with the Addition of Stale Bread, Cornmeal, and Apple Pomace
Authors: Gumul Dorota , Oracz Joanna , Litwinek Dorota , Żyżelewicz Dorota , Zięba Tomasz , Sabat Renata , Wywrocka-Gurgul Anna , Ziobro Rafał
Published: June 2024

The aim of this study was to evaluate the effect of extruded preparations on the bioactive and nutritional properties, vitamin B content, volatile compound profile, and quality of whole wheat bread. Extruded preparations based on stale bread (secondary raw materials) and apple pomace (byproducts) were used as bread additives. It was found that the preparations did not enrich the bread in protein but in health-promoting compounds, especially gallic acid, protocatechuic acid, caffeic acid, p-coumaric acid, rutin, quercetin, and B vitamins. Extruded preparations had a positive effect on the quality of the bread produced, such as yield and cohesiveness, and gave it a pleasant aroma. It was shown that among all the examined bread samples with added extruded preparations of stale bread, the cornmeal and apple pomace bread samples with 15% extruded preparation (containing 55% cornmeal, 30% stale bread, and 15% apple pomace) had sufficient nutritional value, the highest amounts of gallic acid, protocatechuic acid, p-coumaric acid, caffeic acid, rutin, and quercetin; medium amounts of ellagic acid; high antioxidant activity determined in vitro using four methods (by DPPH, ABTS, power (FRAP), and Fe(II) chelating assays); adequate quality; and significant amounts of vitamins, especially B1, B2, and B3. This type of extruded preparation should utilize apple pomace, which is a byproduct, and stale bread, which is a secondary waste. Such a combination is an excellent low-cost, easy, and prospective solution for the baking industry that could be applied to obtain bread with elevated nutritional value and enhanced health potential, as proven in this publication.
Rapid Measurement of Antioxidant Properties of Dendrobium officinale Using Near-Infrared Spectroscopy and Chemometrics
Authors: Cao Xiaoqing , Huang Jing , Chen Jinjing , Niu Ying , Wei Sisi , Tong Haibin , Wu Mingjiang , Yang Yue
Published: June 2024

Dendrobium officinale (D. officinale), often used as a dual-use plant with herbal medicine and food applications, has attracted considerable attention for health-benefiting components and wide economic value. The antioxidant ability of D. officinale is of great significance to ensure its health care value and safeguard consumers’ interests. However, the common analytical methods for evaluating the antioxidant ability of D. officinale are time-consuming, laborious, and costly. In this study, near-infrared (NIR) spectroscopy and chemometrics were employed to establish a rapid and accurate method for the determination of 2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging capacity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity, and ferric reducing antioxidant power (FRAP) in D. officinale. The quantitative models were developed based on the partial least squares (PLS) algorithm. Two wavelength selection methods, namely the genetic algorithm (GA) and competitive adaptive reweighted sampling (CARS) method, were used for model optimization. The CARS-PLS models exhibited superior predictive performance compared to other PLS models. The root mean square errors of cross-validation (RMSECVs) for ABTS, FRAP, and DPPH were 0.44%, 2.64 μmol/L, and 2.06%, respectively. The results demonstrated the potential application of NIR spectroscopy combined with the CARS-PLS model for the rapid prediction of antioxidant activity in D. officinale. This method can serve as an alternative to conventional analytical methods for efficiently quantifying the antioxidant properties in D. officinale.
Protein Nutrition: Understanding Structure, Digestibility, and Bioavailability for Optimal Health
Authors: Ajomiwe Nneka , Boland Mike , Phongthai Suphat , Bagiyal Manisha , Singh Jaspreet , Kaur Lovedeep
Published: June 2024

This review discusses different protein sources and their role in human nutrition, focusing on their structure, digestibility, and bioavailability. Plant-based proteins, such as those found in legumes, nuts, and seeds, may contain anti-nutritional factors that impact their bioavailability apart from structural and compositional differences from animal proteins. Animal proteins are generally highly digestible and nutritionally superior to plant proteins, with higher amino acid bioavailability. Alternative protein sources are also processed in different ways, which can alter their structure and nutritional value, which is also discussed.
Probiotic Insights from the Genomic Exploration of Lacticaseibacillus paracasei Strains Isolated from Fermented Palm Sap
Authors: Sornsenee Phoomjai , Surachat Komwit , Kang Dae-Kyung , Mendoza Remylin , Romyasamit Chonticha
Published: June 2024

This study focused on L. paracasei strains isolated from fermented palm sap in southern Thailand that exhibit potential probiotic characteristics, including antibiotic susceptibility, resistance to gastrointestinal stresses, and antimicrobial activity against various pathogens. However, a thorough investigation of the whole genome sequences of L. paracasei isolates is required to ensure their safety and probiotic properties for human applications. This study aimed to sequence the genome of L. paracasei isolated from fermented palm sap, to assess its safety profile, and to conduct a comprehensive comparative genomic analysis with other Lacticaseibacillus species. The genome sizes of the seven L. paracasei strains ranged from 3,070,747 bp to 3,131,129 bp, with a GC content between 46.11% and 46.17% supporting their classification as nomadic lactobacilli. In addition, the minimal presence of cloud genes and a significant number of core genes suggest a high degree of relatedness among the strains. Meanwhile, phylogenetic analysis of core genes revealed that the strains possessed distinct genes and were grouped into two distinct clades. Genomic analysis revealed key genes associated with probiotic functions, such as those involved in gastrointestinal, oxidative stress resistance, vitamin synthesis, and biofilm disruption. This study is consistent with previous studies that used whole-genome sequencing and bioinformatics to assess the safety and potential benefits of probiotics in various food fermentation processes. Our findings provide valuable insights into the potential use of seven L. paracasei strains isolated from fermented palm sap as probiotic and postbiotic candidates in functional foods and pharmaceuticals.
Classifying Sets of Type (4,n) in PG(3,q)
Authors: Innamorati Stefano
Published: June 2024

In the present work, we classify sets of type (4,n) in PG(3,q). We prove that PG(3,q), apart from the planes of PG(3,3), contains only sets of type (4,n) with standard parameters. Thus, somewhat surprisingly, we conclude that there are no sets of type (4,n) in PG(3,q), q ≠ 3, with non-standard parameters.
Nonlocal Changing-Sign Perturbation Tempered Fractional Sub-Diffusion Model with Weak Singularity
Authors: Zhang Xinguang , Chen Jingsong , Chen Peng , Li Lishuang , Wu Yonghong
Published: June 2024

In this paper, we study the existence of positive solutions for a changing-sign perturbation tempered fractional model with weak singularity which arises from the sub-diffusion study of anomalous diffusion in Brownian motion. By two-step substitution, we first transform the higher-order sub-diffusion model to a lower-order mixed integro-differential sub-diffusion model, and then introduce a power factor to the non-negative Green function such that the linear integral operator has a positive infimum. This innovative technique is introduced for the first time in the literature and it is critical for controlling the influence of changing-sign perturbation. Finally, an a priori estimate and Schauder’s fixed point theorem are applied to show that the sub-diffusion model has at least one positive solution whether the perturbation is positive, negative or changing-sign, and also the main nonlinear term is allowed to have singularity for some space variables.
Development and Characterization of Ethylcellulose Oleogels Based on Pumpkin Seed Oil and Rapeseed Oil
Authors: Ursachi Claudiu-Ștefan , Perța-Crișan Simona , Tolan Iolanda , Chambre Dorina Rodica , Chereji Bianca-Denisa , Condrat Dumitru , Munteanu Florentina-Daniela
Published: June 2024

In contrast to rapeseed oil, pumpkin seed oil has yet to be well investigated in terms of oleogelation, and, to the best of our knowledge, no study related to the use of ethylcellulose (EC) in the structuring of this oil has been identified in the current scientific literature. Therefore, the present study evaluated several oleogels formulated with EC as the oleogelator in different concentrations of 7% (OG7) and 9% (OG9), based on cold-pressed pumpkin seed oil (PO) and refined rapeseed oil (RO), as well as on mixtures of the two oils in different combinations: PO:RO (3:1) (PRO) and PO:RO (1:1) (RPO). Physicochemical properties such as visual appearance, gel formation time (GFT), oil-binding capacity (OBC), oxidative and thermal stability, and textural characteristics were analyzed. Analysis of variance (ANOVA) and Tukey’s honestly significant difference (HSD) were used in the statistical analysis of the data, with a significance level of p < 0.05. EC proved to be an effective structuring agent of the mentioned edible oils; the type of oils and the concentration of oleogelator significantly influenced the characteristics of the obtained oleogels. The 9% EC oleogels exhibited a more rigid structure, with a higher OBC and a reduced GFT. Pumpkin seed oil led to more stable oleogels, while the mixture of pumpkin seed oil with rapeseed oil caused a significant reduction in their mechanical properties and decreased the OBC. After 14 days of storage, all oleogels demonstrated proper oxidative stability within the bounds set by international regulations for edible fats, regardless of the kind of oil and EC concentration. All of the oleogels showed a higher oxidative stability than the oils utilized in their formulation; however, those prepared with cold-pressed pumpkin seed oil indicated a lower level of lipid oxidation among all oleogels. The P-OG9 and PR-OG9 oleogels, which mainly included PO and contained 9% EC, demonstrated the optimum levels of quality in texture, GFT, OBC, and oxidative stability.
Molecular Recognition between Carbon Dioxide and Biodegradable Hydrogel Models: A Density Functional Theory (DFT) Investigation
Authors: Carrascal-Hernandez Domingo Cesar , Mendez-Lopez Maximiliano , Insuasty Daniel , García-Freites Samira , Sanjuan Marco , Márquez Edgar
Published: June 2024

In this research, we explore the potential of employing density functional theory (DFT) for the design of biodegradable hydrogels aimed at capturing carbon dioxide (CO2) and mitigating greenhouse gas emissions. We employed biodegradable hydrogel models, including polyethylene glycol, polyvinylpyrrolidone, chitosan, and poly-2-hydroxymethacrylate. The complexation process between the hydrogel and CO2 was thoroughly investigated at the ωB97X-D/6-311G(2d,p) theoretical level. Our findings reveal a strong affinity between the hydrogel models and CO2, with binding energies ranging from −4.5 to −6.5 kcal/mol, indicative of physisorption processes. The absorption order observed was as follows: chitosan > PVP > HEAC > PEG. Additionally, thermodynamic parameters substantiated this sequence and even suggested that these complexes remain stable up to 160 °C. Consequently, these polymers present a promising avenue for crafting novel materials for CO2 capture applications. Nonetheless, further research is warranted to optimize the design of these materials and assess their performance across various environmental conditions.
The Prevalence of Duplicate Prescription of Oral Antibiotic Drugs in Outpatient Care among People Insured by Corporate Health Insurance Societies in Japan
Authors: Fujimoto Kenichi , Tanihara Shinichi
Published: June 2024

Inappropriate antimicrobial use is a global problem, especially because the use of antimicrobials in excess of appropriate doses is associated with increased antimicrobial resistance. Duplicate prescriptions are an issue contributing to inappropriate antimicrobial use. This study aimed to analyse antibiotic prescriptions during a specific month to examine the frequency of outpatients receiving duplicate antibiotic prescriptions and the associated determinants. Utilizing the Japan Medical Data Centre health insurance claim database, we retrospectively identified 527,110 insured individuals with at least one medicine prescription in October 2014. Data regarding age, gender, antibiotic drug usage, and health insurance status were extracted. Duplicate prescriptions entailed a patient receiving two or more prescriptions of systemic antibiotics from multiple facilities within one month. The risk factors for duplicate antibiotic prescriptions were evaluated using logistic regression analysis. Of the total sample, 131,709 individuals (25.0%) received antibiotics, and 24,529 of these individuals (18.6%) had duplicate prescriptions. Third-generation cephalosporins accounted for the largest proportion of prescriptions (37.4%). Duplicate prescriptions were significantly associated with sex, age, medical facilities, and health insurance status. These findings could help to identify patients at risk of duplicate antibiotic prescriptions, highlighting the need to promote proper antimicrobial use in both patients and medical professionals.
The Application of Cathodoluminescence (CL) for the Characterization of Blue Pigments
Authors: Palamara Eleni , Kesidis Stelios , Cifuentes Laura Tormo , Das Partha Pratim , Nicolopoulos Stavros , Zacharias Nikolaos
Published: June 2024

The combined application of Cathodoluminescence (CL) with Scanning Electron Microscopy (SEM) on paintings and painted surfaces has the potential to identify both organic and inorganic pigments on a micrometre or even nanometre scale. Additionally, the combination with Energy-Dispersive Spectrometry (EDS) allows for a more holistic, elemental, and mineralogical characterization of pigments. In addressing the need for the creation of a robust, open access database of characteristic CL spectra of pigments, a large project has been undertaken, focusing primarily on common organic and inorganic pigments. The present paper focuses on the CL characterization of 10 significant blue pigments in pure powder form: cerulean blue, Egyptian blue, Han blue, indigo, lapis lazuli, Maya blue, phthalo blue, vivianite, ultramarine blue, and zirconium blue. The CL spectra present characteristic bands for most of the pigments, allowing their secure identification, especially when combining the results with the EDS analyses. The effect of binding media and of the mixture of different pigments was also studied, via the analysis of mixtures of pigments with oil painted over canvas. Overall, both the binding medium and the mixture of pigments do not appear to create significant differences in the occurring spectra, thus allowing the identification of individual pigments. EDS and RAMAN spectra are included in order to facilitate comparison with other databases.
Discovering the Sansalvador Villa through the Superposition of Photogrammetric Point Cloud Surveys and Original Jujol Plans
Authors: de Gispert Hernández Jordi , Moliner Nuño Sandra , Sánchez Riera Alberto , Crespo Cabillo Isabel , Pàmies Carles
Published: June 2024

The Sansalvador villa, the first project exclusively designed by Josep Maria Jujol in Barcelona, is a unique architectural complex that piques curiosity about its origins and conception. Its incomplete state, limited documentation, and blend of modernist and organic elements contribute to its exceptional nature. This article delves into its history and conceptualization by examining original documents and conducting a detailed photogrammetric survey of the built architectural complex as it is today. By overlaying new planimetry derived from fieldwork onto the original plans, certain peculiarities, discrepancies, and unforeseen changes emerge, shedding light on Jujol’s creative process. The Sansalvador villa reveals the profound connection between the project and its surroundings, showcasing Jujol’s keen awareness of the site’s pre-existing conditions. His architecture is defined by a critical approach to these conditions, integrating them as essential elements in defining the project’s character.
Efficient In Vitro Propagation of Turpinia arguta and Quantitative Analysis of Its Ligustroflavone and Rhoifolin Content
Authors: Hu Jiangmei , Cai Junhuo , Hu Xinrui , Wang Lijun , Cheng Qiangqiang , Tao Xiuhua
Published: June 2024

Turpinia arguta is an excellent medicinal plant mainly used for the treatment of pharyngitis, tonsillitis, and tonsillar abscesses. However, an efficient regeneration protocol using tissue cultures for T. arguta does not exist. Its main medicinal constituents are flavonoids, particularly ligustroflavone and rhoifolin. Here, we aimed to establish a tissue culture system for T. arguta for the first time using annual stem segments with axillary buds harvested from the field of the Jiangxi Academy of Forestry as explants by dynamically determining the accumulation of effective functional components in the tissue culture plantlets. Orthogonal tests were conducted to compare the effects of different explant disinfection times, media, and exogenous hormone ratios on the induction of the axillary bud growth, successional proliferation, and rooting of T. arguta stem segments. The best explant disinfection effect was achieved by disinfecting the T. arguta explant with 75% ethanol for 50 s, followed by 0.1% mercuric chloride (HgCl2) for 6 min, and the optimal media for successional proliferation and rooting were Murashige and Skoog (MS) + 0.2 mg/L of 6-benzyladenine (6-BA), + 0.03 mg/L of naphthaleneacetic acid (NAA), and ½ MS + 2.5 mg/L of indole-3-butyric acid + 0.5 mg/L of NAA, respectively. The detection of ligustroflavone and rhoifolin in tissue culture plantlets 0, 3, and 5 months after transplanting showed a significant increasing trend and eventually exceeded the content requirements of the 2020 Edition ofChinese Pharmacopoeia for T. arguta. Our findings provide, for the first time, an effective tissue culture system for T. arguta, thereby providing important information to support the germplasm preservation, innovation, and application of T. arguta in the future.
Zebrafish as a Human Muscle Model for Studying Age-Dependent Sarcopenia and Frailty
Authors: Aranda-Martínez Paula , Sayed Ramy K. A. , Fernández-Martínez José , Ramírez-Casas Yolanda , Yang Yang , Escames Germaine , Acuña-Castroviejo Darío
Published: June 2024

Currently, there is an increase in the aging of the population, which represents a risk factor for many diseases, including sarcopenia. Sarcopenia involves progressive loss of mass, strength, and function of the skeletal muscle. Some mechanisms include alterations in muscle structure, reduced regenerative capacity, oxidative stress, mitochondrial dysfunction, and inflammation. The zebrafish has emerged as a new model for studying skeletal muscle aging because of its numerous advantages, including histological and molecular similarity to human skeletal muscle. In this study, we used fish of 2, 10, 30, and 60 months of age. The older fish showed a higher frailty index with a value of 0.250 ± 0.000 because of reduced locomotor activity and alterations in biometric measurements. We observed changes in muscle structure with a decreased number of myocytes (0.031 myocytes/μm2 ± 0.004 at 60 months) and an increase in collagen with aging up to 15% ± 1.639 in the 60-month group, corresponding to alterations in the synthesis, degradation, and differentiation pathways. These changes were accompanied by mitochondrial alterations, such as a nearly 50% reduction in the number of intermyofibrillar mitochondria, 100% mitochondrial damage, and reduced mitochondrial dynamics. Overall, we demonstrated a similarity in the aging processes of muscle aging between zebrafish and mammals.
Molecular Research on Coronavirus: Pathogenic Mechanisms, Antiviral Drugs, and New Vaccines
Authors: Zhang Mengjia , Lang Yifei , Li Wentao
Published: June 2024

Since the COVID-19 outbreak in 2019, five coronaviruses have been found to infect humans, including SARS-CoV (severe acute respiratory syndrome coronavirus) [...]
Colonic Tuft Cells: The Less-Recognized Therapeutic Targets in Inflammatory Bowel Disease and Colorectal Cancer
Authors: Sipos Ferenc , Műzes Györgyi
Published: June 2024

Tuft cells are more than guardian chemosensory elements of the digestive tract. They produce a variety of immunological effector molecules in response to stimulation; moreover, they are essential for defense against protozoa and nematodes. Beyond the description of their characteristics, this review aims to elucidate the potential pathogenic and therapeutic roles of colonic tuft cells in inflammatory bowel disease and colorectal cancer, focusing on their primarily immunomodulatory action. Regarding inflammatory bowel disease, tuft cells are implicated in both maintaining the integrity of the intestinal epithelial barrier and in tissue repair and regeneration processes. In addition to maintaining intestinal homeostasis, they display complex immune-regulatory functions. During the development of colorectal cancer, tuft cells can promote the epithelial-to-mesenchymal transition, alter the gastrointestinal microenvironment, and modulate both the anti-tumor immune response and the tumor microenvironment. A wide variety of their biological functions can be targeted for anti-inflammatory or anti-tumor therapies; however, the adverse side effects of immunomodulatory actions must be strictly considered.
Map-Based Cloning and Characterization of a Major QTL Gene, FfR1, Which Confers Resistance to Rice Bakanae Disease
Authors: Ji Hyeonso , Cheon Kyeong-Seong , Shin Yunji , Lee Chaewon , Son Seungmin , Oh Hyoja , Yoon Dong-Kyung , Lee Seoyeon , Cho Mihyun , Jun Soojin , Lee Gang-Seob , Baek Jeongho , Kim Song Lim , Ahn Il-Pyung , Oh Jae-Hyeon , Yoon Hye-Jin , Cha Young-Soon , Kim Kyung-Hwan
Published: June 2024

Bakanae disease (BD), caused by the fungal pathogen Fusarium fujikuroi, is a serious threat to rice production worldwide. Breeding elite rice varieties resistant to BD requires the identification of resistance genes. Previously, we discovered a resistant quantitative trait locus (QTL), qFfR1, in a Korean japonica rice variety, Nampyeong. In this study, we fine-mapped qFfR1 with a Junam*4/Nampyeong BC3F3 population and delimited its location to a 37.1 kb region on chromosome 1. Complementation experiments with seven candidate genes in this region revealed that OsI_02728 is the gene for qFfR1. This gene encodes a protein with a typical leucine-rich repeat (LRR) receptor-like protein structure. RNA-sequencing-based transcriptomic analysis revealed that FfR1 induces the transcription of defense genes, including lignin and terpenoid biosynthesis genes, pathogenesis-related genes, and thionin genes. These results may facilitate investigations into the molecular mechanisms underlying BD resistance, including molecular patterns of Fusarium fujikuroi interacting with FfR1 and players working in signal transduction pathways downstream of FfR1, and the breeding of new BD-resistant varieties by providing a BD resistance gene with its precise selection marker. This will contribute to efficient control of BD, which is becoming more prevalent according to temperature rises due to climate change.
Streptococcus gordonii Supragingival Bacterium Oral Infection-Induced Periodontitis and Robust miRNA Expression Kinetics
Authors: Aravindraja Chairmandurai , Jeepipalli Syam , Duncan William D. , Vekariya Krishna Mukesh , Rahaman Shaik O. , Chan Edward K. L. , Kesavalu Lakshmyya
Published: June 2024

Streptococcus gordonii (S. gordonii, Sg) is one of the early colonizing, supragingival commensal bacterium normally associated with oral health in human dental plaque. MicroRNAs (miRNAs) play an important role in the inflammation-mediated pathways and are involved in periodontal disease (PD) pathogenesis. PD is a polymicrobial dysbiotic immune-inflammatory disease initiated by microbes in the gingival sulcus/pockets. The objective of this study is to determine the global miRNA expression kinetics in S. gordonii DL1-infected C57BL/6J mice. All mice were randomly divided into four groups (n = 10 mice/group; 5 males and 5 females). Bacterial infection was performed in mice at 8 weeks and 16 weeks, mice were euthanized, and tissues harvested for analysis. We analyzed differentially expressed (DE) miRNAs in the mandibles of S. gordonii-infected mice. Gingival colonization/infection by S. gordonii and alveolar bone resorption (ABR) was confirmed. All the S. gordonii-infected mice at two specific time points showed bacterial colonization (100%) in the gingival surface, and a significant increase in mandible and maxilla ABR (p < 0.0001). miRNA profiling revealed 191 upregulated miRNAs (miR-375, miR-34b-5p) and 22 downregulated miRNAs (miR-133, miR-1224) in the mandibles of S. gordonii-infected mice at the 8-week mark. Conversely, at 16 weeks post-infection, 10 miRNAs (miR-1902, miR-203) were upregulated and 32 miRNAs (miR-1937c, miR-720) were downregulated. Two miRNAs, miR-210 and miR-423-5p, were commonly upregulated, and miR-2135 and miR-145 were commonly downregulated in both 8- and 16-week-infected mice mandibles. Furthermore, we employed five machine learning (ML) algorithms to assess how the number of miRNA copies correlates with S. gordonii infections in mice. In the ML analyses, miR-22 and miR-30c (8-week), miR-720 and miR-339-5p (16-week), and miR-720, miR-22, and miR-339-5p (combined 8- and 16-week) emerged as the most influential miRNAs.
In Vitro Hypoxia/Reoxygenation Induces Mitochondrial Cardiolipin Remodeling in Human Kidney Cells
Authors: Strazdauskas Arvydas , Trumbeckaite Sonata , Jakstas Valdas , Dambrauskiene Justina , Mieldazyte Ausra , Klimkaitis Kristupas , Baniene Rasa
Published: June 2024

Renal ischemia/reperfusion is a serious condition that not only causes acute kidney injury, a severe clinical syndrome with high mortality, but is also an inevitable part of kidney transplantation or other kidney surgeries. Alterations of oxygen levels during ischemia/reperfusion, namely hypoxia/reoxygenation, disrupt mitochondrial metabolism and induce structural changes that lead to cell death. A signature mitochondrial phospholipid, cardiolipin, with many vital roles in mitochondrial homeostasis, is one of the key players in hypoxia/reoxygenation-induced mitochondrial damage. In this study, we analyze the effect of hypoxia/reoxygenation on human renal proximal tubule epithelial cell (RPTEC) cardiolipins, as well as their metabolism and mitochondrial functions. RPTEC cells were placed in a hypoxic chamber with a 2% oxygen atmosphere for 24 h to induce hypoxia; then, they were replaced back into regular growth conditions for 24 h of reoxygenation. Surprisingly, after 24 h, hypoxia cardiolipin levels substantially increased and remained higher than control levels after 24 h of reoxygenation. This was explained by significantly elevated levels of cardiolipin synthase and lysocardiolipin acyltransferase 1 (LCLAT1) gene expression and protein levels. Meanwhile, hypoxia/reoxygenation decreased ADP-dependent mitochondrial respiration rates and oxidative phosphorylation capacity and increased reactive oxygen species generation. Our findings suggest that hypoxia/reoxygenation induces cardiolipin remodeling in response to reduced mitochondrial oxidative phosphorylation in a way that protects mitochondrial function.
Novel Compound MMV1804559 from the Global Health Priority Box Exhibits In Vitro and In Vivo Activity against Madurella mycetomatis
Authors: Ma Jingyi , Eadie Kimberly , Schippers Marij , Fahal Ahmed , Laleu Benoît , Verbon Annelies , van de Sande Wendy W. J.
Published: June 2024

Objectives: Eumycetoma is a neglected tropical disease (NTD) characterized by subcutaneous lesions and the formation of grains. Attempts to treat eumycetoma involve a combination of antifungal treatment and surgery, although the outcome is frequently disappointing. Therefore, there is a need to identify novel antifungal drugs to treat eumycetoma. In this respect, Medicines for Malaria Venture (MMV) has assembled libraries of compounds for researchers to use in drug discovery research against NTD. Therefore, we screened two MMVOpen compound libraries to identify novel leads for eumycetoma. Methods: A total of 400 compounds from the COVID Box and the Global Health Priority Box were screened in vitro at 100 µM and 25 µM against the most common causative agents of eumycetoma, namely Madurella mycetomatis and Falciformispora senegalensis, and the resulting IC50 and MIC50 values were obtained. Compounds with an IC50 < 8 µM were identified for possible in vivo efficacy studies using an M. mycetomatis grain model in Galleria mellonella larvae. Results: Out of the 400 compounds, 22 were able to inhibit both M. mycetomatis and F. senegalensis growth at 100 µM and 25 µM, with compounds MMV1593278, MMV020335, and MMV1804559 being selected for in vivo testing. Of these three, only the pyrazolopyrimidine derivative MMV1804559 was able to prolong the survival of M. mycetomatis-infected G. mellonella larvae. Furthermore, the grains in MMV1804559-treated larvae were significantly smaller compared to the PBS-treated group. Conclusion: MMV1804559 shows promising in vitro and in vivo activity against M. mycetomatis.
Mitochondrial Oxidative Stress Regulates FOXP3+ T-Cell Activity and CD4-Mediated Inflammation in Older Adults with Frailty
Authors: Gill Jappreet Singh , Bansal Benu , Guo Kai , Huang Fang , Singh Harpreet , Hur Junguk , Khan Nadeem , Mathur Ramkumar
Published: June 2024

In healthy older adults, the immune system generally preserves its response and contributes to a long, healthy lifespan. However, rapid deterioration in immune regulation can lead to chronic inflammation, termed inflammaging, which accelerates pathological aging and diminishes the quality of life in older adults with frailty. A significant limitation in current aging research is the predominant focus on comparisons between young and older populations, often overlooking the differences between healthy older adults and those experiencing pathological aging. Our study elucidates the intricate immunological dynamics of the CD4/Treg axis in frail older adults compared to comparable age-matched healthy older adults. By utilizing publicly available RNA sequencing and single-cell RNA sequencing (scRNAseq) data from peripheral blood mononuclear cells (PBMCs), we identified a specific Treg cell subset and transcriptional landscape contributing to the dysregulation of CD4+ T-cell responses. We explored the molecular mechanisms underpinning Treg dysfunction, revealing that Tregs from frail older adults exhibit reduced mitochondrial protein levels, impairing mitochondrial oxidative phosphorylation. This impairment is driven by the TNF/NF-kappa B pathway, leading to cumulative inflammation. Further, we gained a deeper understanding of the CD4/Treg axis by predicting the effects of gene perturbations on cellular signaling networks. Collectively, these findings highlight the age-related relationship between mitochondrial dysfunction in the CD4/Treg axis and its role in accelerating aging and frailty in older adults. Targeting Treg dysfunction offers a critical basis for developing tailored therapeutic strategies aimed at improving the quality of life in older adults.
Increased Expression of Orexin-A in Patients Affected by Polycystic Kidney Disease
Authors: Nigro Ersilia , D’Arco Daniela , Moscatelli Fiorenzo , Pisani Antonio , Amicone Maria , Riccio Eleonora , Capuano Ivana , Argentino Francesca , Monda Marcellino , Messina Giovanni , Daniele Aurora , Polito Rita
Published: June 2024

Orexin-A is a neuropeptide product of the lateral hypothalamus that acts on two receptors, OX1R and OX2R. The orexinergic system is involved in feeding, sleep, and pressure regulation. Recently, orexin-A levels have been found to be negatively correlated with renal function. Here, we analyzed orexin-A levels as well as the incidence of SNPs in the hypocretin neuropeptide precursor (HCRT) and its receptors, HCRTR1 and HCRTR2, in 64 patients affected by autosomal dominant polycystic kidney disease (ADPKD) bearing truncating mutations in the PKD1 or PKD2 genes. Twenty-four healthy volunteers constituted the control group. Serum orexin-A was assessed by ELISA, while the SNPs were investigated through Sanger sequencing. Correlations with the main clinical features of PKD patients were assessed. PKD patients showed impaired renal function (mean eGFR 67.8 ± 34.53) and a statistically higher systolic blood pressure compared with the control group (p < 0.001). Additionally, orexin-A levels in PKD patients were statistically higher than those in healthy controls (477.07 ± 69.42 pg/mL vs. 321.49 ± 78.01 pg/mL; p < 0.001). Furthermore, orexin-A inversely correlated with blood pressure (p = 0.0085), while a direct correlation with eGFR in PKD patients was found. None of the analyzed SNPs showed any association with orexin-A levels in PKD. In conclusion, our data highlights the emerging role of orexin-A in renal physiology and its potential relevance to PKD. Further research is essential to elucidate the intricate mechanisms underlying orexin-A signaling in renal function and its therapeutic implications for PKD and associated cardiovascular complications.
A New Hope for the Treatment of Atrial Fibrillation: Application of Pulsed-Field Ablation Technology
Authors: Wang Zhen , Liang Ming , Sun Jingyang , Zhang Jie , Han Yaling
Published: June 2024

In recent years, the prevalence of and mortality associated with cardiovascular diseases have been rising in most countries and regions. AF is the most common arrhythmic condition, and there are several treatment options for AF. Pulmonary vein isolation is an effective treatment for AF and is the cornerstone of current ablation techniques, which have one major limitation: even when diagnosed and treated at a facility that specializes in ablation, patients have a greater chance of recurrence. Therefore, there is a need to develop better ablation techniques for the treatment of AF. This article first compares the current cryoablation (CBA) and radiofrequency ablation (RFA) techniques for the treatment of AF and discusses the utility and advantages of the development of pulsed-field ablation (PFA) technology. The current research on PFA is summarized from three perspectives, namely, simulation experiments, animal experiments, and clinical studies. The results of different stages of experiments are summarized, especially during animal studies, where pulmonary vein isolation was carried out effectively without causing injury to the phrenic nerve, esophagus, and pulmonary veins, with higher safety and shorter incision times. This paper focuses on a review of various a priori and clinical studies of this new technique for the treatment of AF.
Leveraging Cancer Phenotypic Plasticity for Novel Treatment Strategies
Authors: Ramisetty Sravani , Subbalakshmi Ayalur Raghu , Pareek Siddhika , Mirzapoiazova Tamara , Do Dana , Prabhakar Dhivya , Pisick Evan , Shrestha Sagun , Achuthan Srisairam , Bhattacharya Supriyo , Malhotra Jyoti , Mohanty Atish , Singhal Sharad S. , Salgia Ravi , Kulkarni Prakash
Published: June 2024

Cancer cells, like all other organisms, are adept at switching their phenotype to adjust to the changes in their environment. Thus, phenotypic plasticity is a quantitative trait that confers a fitness advantage to the cancer cell by altering its phenotype to suit environmental circumstances. Until recently, new traits, especially in cancer, were thought to arise due to genetic factors; however, it is now amply evident that such traits could also emerge non-genetically due to phenotypic plasticity. Furthermore, phenotypic plasticity of cancer cells contributes to phenotypic heterogeneity in the population, which is a major impediment in treating the disease. Finally, plasticity also impacts the group behavior of cancer cells, since competition and cooperation among multiple clonal groups within the population and the interactions they have with the tumor microenvironment also contribute to the evolution of drug resistance. Thus, understanding the mechanisms that cancer cells exploit to tailor their phenotypes at a systems level can aid the development of novel cancer therapeutics and treatment strategies. Here, we present our perspective on a team medicine-based approach to gain a deeper understanding of the phenomenon to develop new therapeutic strategies.