bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Bioactive Edible Film and Coating Obtained from Spirogyra sp. Extract Applied for Enhancing Shelf Life of Fresh Products
Authors: Soiklom Siriwan , Siri-anusornsak Wipada , Petchpoung Krittaya , Soiklom Sumpan , Maneeboon Thanapoom
Published: February 2025

The growing interest in environmentally friendly food packaging has led to the development of bio-edible alternatives. This study developed novel, edible, active films and coatings to enhance the shelf life of fresh products. Crude bioactive algal extract (CBAE) was obtained from the ethanol extraction of Spirogyra sp. and incorporated into chitosan-based films and coatings at varying concentrations. The CBAE was rich in phenolic compounds and had antioxidant activity and potential antibacterial properties. The films were prepared using a solvent-casting method and characterized for their biochemical and physical properties. The incorporation of CBAE enhanced the antioxidant activity and improved the tensile strength of the films by 80%. Additionally, film transparency and water vapor permeability were reduced by 13% and 50%, respectively, compared to the control. The developed CBAE coating solution exhibited biocompatibility with human colon adenocarcinoma (HT-29) and mouse subcutaneous connective tissue (L929) fibroblast cells. A shelf-life evaluation using a coating-dipping method on okra showed that the CBAE-coated samples maintained better weight retention and firmness than the uncoated samples over 5 days of storage at ambient temperature. Based on these findings, the CBAE-based edible films and coatings could serve as sustainable alternatives for extending the shelf life of fresh products.
Clean Label Approaches in Cheese Production: Where Are We?
Authors: Fernandes Jaime , Gomes Sandra , Reboredo Fernando H. , Pintado Manuela E. , Amaral Olga , Dias João , Alvarenga Nuno
Published: February 2025

The Clean Label concept has gained significant traction in the cheese industry due to consumer preferences for minimally processed cheeses free from synthetic additives. This review explores different approaches for applying Clean Label principles to the cheese industry while maintaining food safety, sensory quality, and shelf life. Non-thermal technologies, such as high-pressure processing (HPP), pulsed electric fields (PEF), ultra-violet (UV), and visible light (VL), are among the most promising methods that effectively control microbial growth while preserving the nutritional and functional properties of cheese. Protective cultures, postbiotics, and bacteriophages represent microbiological strategies that are natural alternatives to conventional preservatives. Another efficient approach involves plant extracts, which contribute to microbial control, and enhance cheese functionality and potential health benefits. Edible coatings, either alone or combined with other methods, also show promising applications. Despite these advantages, several challenges persist: higher costs of production and technical limitations, possible shorter shelf-life, and regulatory challenges, such as the absence of standardized Clean Label definitions and compliance complexities. Further research is needed to develop and refine Clean Label formulations, especially regarding bioactive peptides, sustainable packaging, and advanced microbial control techniques. Addressing these challenges will be essential for expanding Clean Label cheese availability while ensuring product quality and maintaining consumer acceptance.
Integrating Microalgal Chlorella Biomass and Biorefinery Residues into Sustainable Agriculture and Food Production: Insights from Lettuce Cultivation
Authors: Wichaphian Antira , Kamngoen Apiwit , Pathom-aree Wasu , Maneechote Wageeporn , Khuendee Tawanchai , Chromkaew Yupa , Cheirsilp Benjamas , Shyu Douglas J. H. , Srinuanpan Sirasit
Published: February 2025

Microalgal biomass offers a promising biofertilizer option due to its nutrient-rich composition, adaptability, and environmental benefits. This study evaluated the potential of microalgal-based biofertilizers—microalgal Chlorella biomass, de-oiled microalgal biomass (DMB), and de-oiled and de-aqueous extract microalgal biomass (DAEMB)—in enhancing lettuce growth, soil nutrient dynamics, and microbial community composition. Lettuce seedlings were cultivated with these biofertilizers, and plant growth parameters, photosynthetic pigments, and nitrogen uptake were assessed. Soil incubation experiments further examined nutrient mineralization rates, while DNA sequencing analyzed shifts in rhizosphere microbial communities. Lettuce grown with these biofertilizers exhibited improved growth parameters compared to controls, with Chlorella biomass achieving a 31.89% increase in shoot length, 27.98% in root length, and a 47.33% increase in fresh weight. Chlorophyll a and total chlorophyll levels increased significantly in all treatments, with the highest concentrations observed in the Chlorella biomass treatment. Soil mineralization studies revealed that DMB and DAEMB provided a gradual nitrogen release, while Chlorella biomass exhibited a rapid nutrient supply. Microbial community analyses revealed shifts in bacterial and fungal diversity, with increased abundance of nitrogen-fixing and nutrient-cycling taxa. Notably, fungal diversity was enriched in biomass and DAEMB treatments, enhancing soil health and reducing pathogenic fungi. These findings highlight microalgal biofertilizers’ potential to enhance soil fertility, plant health, and sustainable resource use in agriculture.
Low Glycemic Index Biscuits Enriched with Beetroot Powder as a Source of Betaine and Mineral Nutrients
Authors: Mitrevski Jasmina , Pantelić Nebojša Đ. , Laličić-Petronijević Jovanka , Kojić Jovana S. , Zlatanović Snežana , Gorjanović Stanislava , Avramov Stevan , Dodevska Margarita S. , Antić Vesna V.
Published: February 2025

This study aimed to evaluate the potential of beetroot powder (BP) as a functional ingredient in biscuits by investigating its effects on nutritional composition, sensory properties, and glycemic response. The primary goal was to determine whether BP could serve as a natural alternative to synthetic additives while maintaining product stability and consumer acceptability. Biscuits were formulated by replacing spelt flour with 15, 20, and 25% BP. The functional impact of the BP was assessed based on betaine content, macro- and microelements, glycemic index (GI), and acrylamide concentration. Thermal analysis (DSC and TGA) and water activity measurements confirmed the BP’s stability during six months of storage. Increased BP content led to higher betaine levels and mineral enrichment, particularly with potassium and phosphorus among the macroelements and zinc among the microelements. Sensory analysis identified biscuits with 20% BP as the most preferred, maintaining acceptable ratings even after six months. Hardness initially increased with BP incorporation but decreased over time (p < 0.05). The acrylamide content in the BP-enriched biscuits was significantly lower than in control samples and well below the reference safety threshold. Notably, consuming beetroot biscuits did not trigger a sharp postprandial glucose spike, with the GI of the most acceptable sample (20% BP) measured at 49 ± 11. These findings confirm that BP improves the nutritional and sensory characteristics of biscuits while ensuring product safety and stability, supporting its application as a natural functional ingredient in confectionery products.
Metagenomic Characterization of the Maerua crassifolia Soil Rhizosphere: Uncovering Microbial Networks for Nutrient Acquisition and Plant Resilience in Arid Ecosystems
Authors: Alharbi Sumayah M. , Al-Sulami Nadiah , Al-Amrah Hadba , Anwar Yasir , Gadah Ola A. , Bahamdain Lina Ahmed , Al-Matary Mohammed , Alamri Amnah M. , Bahieldin Ahmed
Published: February 2025

Background/Objectives:Maerua crassifolia, a threatened medicinal species endemic to drylands, exhibits a pronounced drought sensitivity. Despite the critical role of microorganisms, particularly bacteria and fungi, the microbial consortia in M. crassifolia’s rhizosphere remain underexplored. Methods: Metagenomic whole genome shotgun sequencing (WGS) was employed to elucidate the taxonomic composition of bacterial and fungal communities inhabiting the soil rhizosphere of M. crassifolia. Results: The data revealed a marked predominance of bacterial genomes relative to fungal communities, as evidenced by non-redundant gene analysis. Notably, arbuscular mycorrhizal fungi (AMF), specifically Rhizophagus clarus, Rhizophagus irregularis and Funneliformis geosporum, are key rhizosphere colonizers. This study confirmed the presence of phosphate-solubilizing bacteria (PSB), such as Sphingomonas spp., Cyanobacteria and Pseudomonadota, underscoring the critical role of these microorganisms in the phosphorus cycle. Additionally, the study uncovered the presence of previously uncharacterized species within the phylum Actinobacteria, as well as unidentified taxa from the Betaproteobacteria, Gemmatimonadota and Chloroflexota phyla, which may represent novel microbial taxa with potential plant growth-promoting properties. Conclusions: Findings suggest a complex, symbiotic network where AMF facilitate phosphorus uptake through plant–root interactions. In a tripartite symbiosis, PSB enhance inorganic phosphorus solubilization, increasing bioavailability, which AMF assimilate and deliver to plant roots, optimizing nutrition. This bacterial–fungal interplay is essential for plant resilience in arid environments. Future investigations should prioritize the isolation and characterization of underexplored microbial taxa residing in the rhizosphere of M. crassifolia, with particular emphasis on members of the Actinobacteria, Betaproteobacteria, Gemmatimonadota and Chloroflexota phyla to uncover their roles in nutrient acquisition and sustainability.
Decisions, Decisions: Observations of Resource Allocation Under Consumer-Directed Care
Authors: Kenny Danelle , Nguyen Kim-Huong , Breig Zachary , Friesen Lana , Comans Tracy
Published: February 2025

Introduction: Resource trade-offs are a universal feature of decision-making in healthcare. Public funding for home care is an example of a complex resource allocation decision, requiring balance between the needs of the individual and the capacity of the welfare system to meet those needs across the population. Under consumer-directed care policies, responsibility for resource allocation decisions rests with the care recipient, but there is no existing measure of allocative efficiency resulting from these consumer-led decisions. Our research considers resource allocation decisions by home care package recipients under consumer-directed care and evaluates the consistency of consumer-directed resource allocation with medically identified recommendations. Method: Retrospective cohort analysis of twenty home care package resource allocations made by home care package recipients in South-East Queensland, compared to associated medically identified needs and discussions with a potential service provider. Findings: Resource allocation decisions in the Australian home care setting are complex, multi-faceted, and made in highly uncertain environments. There are significant differences between services and equipment recommendations made by assessment teams, service providers, and home care recipient choices. Discussion: Awareness of the decision-making process and resulting decisions provides a foundation for future research to simplify decision-making for home care package recipients without sacrificing autonomy, leading to improved resource allocation efficiency and home care program outcomes. Conclusion: Consumer-directed care is a globally popular policy position to allocate public funds related to health care needs, despite uncertainty around the impact of this policy on program outcomes. Our analysis suggests further understanding of factors influencing resource allocation decisions is needed to define appropriate supports for effective decision-making in home care resource allocation, and further research effort is required to determine efficient resource allocation to inform policy changes, irrespective of the decision-maker.
Nutrient Balance of Citrus Across the Mandarin Belts of India
Authors: Srivastava Anoop Kumar , Huchche Ambadas Dattatray , Parent Leon-Etienne , Malhotra Suresh Kumar , Ziogas Vasileios , Baishya Lohit Kumar
Published: February 2025

India is a major producer of mandarin oranges. However, the average fruit yield remains below potential due in part to multiple nutrient deficiencies. Our objective was to elaborate compositional nutrient diagnosis (CND) log-ratio standards accounting for nutrient interactions and the dilution the leaf tissue. We hypothesized that equally or unequally weighted dual nutrient log ratios integrated into centered log ratios (clr) or weighted log ratios (wlr) influence the accuracy of the CND diagnosis. The database comprised 494 observations on ‘Nagpur’, ‘Khasi’, and ‘Kinnow’ cultivars surveyed in contrasting agroecosystems of India. Weights were provided by gain ratios that indicated the importance of the dual log ratio on crop performance. The cutoff yield was set at the upper high-yield quarter for each variety. Centered log ratios (clrs) and weighted log ratios (wlrs) returned accuracies of 0.7–0.8 depending on the machine learning classification model. The gain ratios were not contrasted enough to make a difference between clr and wlr. We derived clr and wlr nutrient standards following the Gradient Boosting model. In a case study, the clr and wlr returned similar diagnoses. The capacity of clr and wlr to generalize to unseen cases and correct nutrient imbalance should be further verified in fertilizer trials. The diagnosis could also be conducted at a local scale, thanks to the Euclidian geometry and additivity of clr and wlr variables.
COVID-19 and Parasitic Co-Infection: A Hypothetical Link to Pulmonary Vascular Disease
Authors: Nyasulu Peter S. , Tamuzi Jacques L. , Oliveira Rudolf K. F. , Oliveira Suellen D. , Petrosillo Nicola , de Jesus Perez Vinicio , Dhillon Navneet , Butrous Ghazwan
Published: February 2025

Background/Objectives: Before the Coronavirus disease 2019 (COVID-19) era, the global prevalence of pulmonary arterial hypertension (PAH) was between 0.4 and 1.4 per 100,000 people. The long-term effects of protracted COVID-19 associated with pulmonary vascular disease (PVD) risk factors may increase this prevalence. According to preliminary data, the exact prevalence of early estimates places the prevalence of PVD in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at 22%, although its predictive value remains unknown. PVD caused by COVID-19 co-infections is understudied and underreported, and its future impact is unclear. However, due to COVID-19/co-infection pathophysiological effects on pulmonary vascularization, PVD mortality and morbidity may impose a genuine concern—both now and in the near future. Based on reported studies, this literature review focused on the potential link between COVID-19, parasitic co-infection, and PVD. This review article also highlights hypothetical pathophysiological mechanisms between COVID-19 and parasitic co-infection that could trigger PVD. Methods: We conducted a systematic literature review (SLR) searching peer-reviewed articles, including link between COVID-19, parasitic co-infection, and PVD. Results: This review hypothesized that multiple pathways associated with pathogens such as underlying schistosomiasis, human immunodeficiency virus (HIV), pulmonary tuberculosis (PTB), pulmonary aspergillosis, Wuchereria bancrofti, Clonorchis sinensis, paracoccidioidomycosis, human herpesvirus 8, and scrub typhus coupled with acute or long COVID-19, may increase the burden of PVD and worsen its mortality in the future. Conclusions: Further experimental studies are also needed to determine pathophysiological pathways between PVD and a history of COVID-19/co-infections.
Correction: Zeng et al. Algicidal Efficiency and Genotoxic Effects of Phanerochaete chrysosporium against Microcystis aeruginosa. Int. J. Environ. Res. Public Health 2020, 17, 4029
Authors: Zeng Guoming , Zhang Maolan , Gao Pei , Wang Jiale , Sun Da
Published: February 2025

In the original publication [...]
The Socio-Cultural Construction of Menstruation in the Ghanaian Context: A Qualitative Study of the Perspectives of Parents, Teachers, and Adolescent Girls
Authors: Gbogbo Sitsofe , Wuresah Israel , Gbogbo Emmanuel , Axame Wisdom Kudzo , Klutse Priscilla , Dowou Robert Kokou , Mantey Sarah Odi , Ayitey Sarah Abena Yeome , Boateng Ishmael , Nelson Paramount Eli , Kugbey Nuworza , Doku Victor Christian Korley , Hennegan Julie , Baiden Frank , Binka Fred Newton
Published: February 2025

(1) Background: Menstruation, experienced by 1.8 billion girls and women globally, is often misunderstood and surrounded by taboos and misconceptions, particularly in low-income countries like Ghana. This study explores the Ghanaian socio-cultural representation of menstruation and the cultural experiences of young girls during menarche. (2) Methods: This qualitative exploratory study was conducted in five Senior High Schools in Ghana’s Volta Region, using purposive and convenience sampling. Fifteen Focus Group Discussions (FGDs) were conducted, including five FGDs each for female students, teachers, and parents, with 10–12 participants per group. All FGDs were audio-recorded, transcribed, translated, and imported into MAXQDA 2022 for thematic analysis. (3) Results: This study identified various socio-cultural beliefs and practices surrounding menstruation in Ghana, including the celebration of menarche, viewing menstrual blood as unclean, and cultural taboos like household, religious, and social restrictions. (4) Conclusion: Despite shifting beliefs and practices, cultural and social practices/restrictions regarding menstruation are persistent in the Volta Region of Ghana, and these practices often determine how society interacts with menstruating women. These practices often determine how society interacts with menstruating girls and women and hinder optimal menstrual health and hygiene.
Special Issue “Antifungal Drug Discovery: Progresses, Challenges, Opportunities”
Authors: Biersack Bernhard
Published: February 2025

The considerable health risks associated with fungal infections are continuously rising, thereby requiring proper and efficient antifungal treatment options [...]
Optimization of Surfactant-Mediated Green Extraction of Phenolic Compounds from Grape Pomace Using Response Surface Methodology
Authors: Atanacković Krstonošić Milica , Sazdanić Darija , Mikulić Mira , Ćirin Dejan , Milutinov Jovana , Krstonošić Veljko
Published: February 2025

Grape pomace is a by-product abundant in phenolic compounds that can be used in the food, cosmetic, and pharmaceutical industries. For the efficient extraction of such compounds, an aqueous solution of non-ionic surfactant Brij S20 was applied as a green extraction medium, and the optimization was performed using surface response methodology. The effects of four independent factors (surfactant concentration, time, pH, and solvent-to-material ratio) were evaluated, and total phenolic content (TPC), DPPH radical inhibition, and selected polyphenol compound concentrations were analyzed as responses. Using response surface methodology (RSM), five regression equations were derived and good adequacy of the models was confirmed. The solvent-to-material (SM) ratio was the most influential factor. Surfactant concentration of 3% (m/V), extraction time of 120 min, pH value of 4.06, and SM ratio of 50 mL/g were determined as optimum conditions to maximize all responses. Under the optimal conditions, the mean validated values obtained for TPC, DPPH, gallic acid, catechin, and quercetin concentrations were 968.50 ± 37.06 mg GAE/L, 61.41 ± 7.13%, 5.10 ± 0.05 mg/L, 10.62 ± 0.79 mg/L, and 6.04 ± 0.10 mg/L, respectively. Furthermore, the established conditions were applied for the extraction of phenolic compounds from grape pomace of four grape varieties. The proposed extraction method proved effective, providing extracts rich in polyphenols suitable for further applications.
Single-Cell Sequencing: Genomic and Transcriptomic Approaches in Cancer Cell Biology
Authors: Ortega-Batista Ana , Jaén-Alvarado Yanelys , Moreno-Labrador Dilan , Gómez Natasha , García Gabriela , Guerrero Erika N.
Published: February 2025

This article reviews the impact of single-cell sequencing (SCS) on cancer biology research. SCS has revolutionized our understanding of cancer and tumor heterogeneity, clonal evolution, and the complex interplay between cancer cells and tumor microenvironment. SCS provides high-resolution profiling of individual cells in genomic, transcriptomic, and epigenomic landscapes, facilitating the detection of rare mutations, the characterization of cellular diversity, and the integration of molecular data with phenotypic traits. The integration of SCS with multi-omics has provided a multidimensional view of cellular states and regulatory mechanisms in cancer, uncovering novel regulatory mechanisms and therapeutic targets. Advances in computational tools, artificial intelligence (AI), and machine learning have been crucial in interpreting the vast amounts of data generated, leading to the identification of new biomarkers and the development of predictive models for patient stratification. Furthermore, there have been emerging technologies such as spatial transcriptomics and in situ sequencing, which promise to further enhance our understanding of tumor microenvironment organization and cellular interactions. As SCS and its related technologies continue to advance, they are expected to drive significant advances in personalized cancer diagnostics, prognosis, and therapy, ultimately improving patient outcomes in the era of precision oncology.
The Role of Adenogenesis Factors in the Pathogenesis of Endometriosis
Authors: Signorile Pietro G. , Baldi Alfonso , Viceconte Rosa , Boccellino Mariarosaria
Published: February 2025

Endometriosis is a pathological condition characterized by the presence of the endometrial tissue, outside the uterine cavity. It affects nearly 10% of women of reproductive age and is responsible for infertility, chronic pain, and the weakening of the quality of life. Various pathogenetic mechanisms have been suggested; however, the essential pathogenesis of endometriosis remains insufficiently comprehended. A comprehensive literature search was conducted in databases such as PubMed, Scopus, and Web of Science up to December 2024. Inclusion criteria encompassed studies investigating the pathogenetic mechanisms of endometriosis, while exclusion criteria included reviews, case reports, and studies lacking primary data. The analyzed studies explored multiple pathogenetic mechanisms, including retrograde menstruation, coelomic metaplasia, embryological defects, stem cell involvement, and epigenetic modifications. Special emphasis was placed on the role of uterine adenogenesis factors in the development and progression of endometriosis. A deeper understanding of the various pathogenetic mechanisms underlying endometriosis is crucial for advancing targeted therapeutic strategies. Further research into uterine adenogenesis factors may provide new insights into the disease’s pathophysiology and pave the way for novel treatment approaches.
Vicenin-2 Hinders Pro-Inflammatory Response via Targeting the CaMKKβ-AMPK-SIRT1 Axis in Lipopolysaccharide-Stressed THP-1 Cells
Authors: Maugeri Alessandro , Russo Caterina , Patanè Giuseppe Tancredi , Farina Martina , Rapisarda Antonio , Masullo Mariorosario , Navarra Michele
Published: February 2025

Plant secondary metabolites are known to be valuable agents to hamper inflammation owing to their multiple mechanisms of action. This study investigates the molecular mechanisms underlying the anti-inflammatory effects of vicenin-2 in lipopolysaccharide (LPS)-stressed THP-1 cells. After ascertaining the safety of vicenin-2 in our in vitro model, we assessed the anti-inflammatory potential of this flavonoid. Indeed, it counteracted the increase of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels, as well as the overexpression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 caused by the exposure of THP-1 cells to LPS. Acknowledged the role of SIRT1 in the inflammatory process, we focused our attention on this enzyme. Our results showed that LPS dramatically decreased the expression of SIRT1, whereas vicenin-2 restored the levels of this enzyme to those of unexposed cells. These effects were also observed in terms of acetylated p53, a SIRT1 substrate. Notably, we observed that vicenin-2 did not act as a direct activator of SIRT1. Therefore, we investigated the potential involvement of AMP-activated protein kinase (AMPK), an upstream activator of SIRT1. Of note, by blocking AMPK by dorsomorphin, the protective effects of vicenin-2 on SIRT1 expression and activity were lost, suggesting the engagement of this kinase. Consequently, the blockage of AMPK caused a downstream loss of the anti-inflammatory effect of vicenin-2, which was no longer able to decrease both the activation of nuclear factor (NF)-κB and the production of cytokines induced by LPS. Finally, docking simulation suggested that vicenin-2 might act as an activator of Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ), one of the regulators of AMPK. Overall, our results suggest that the anti-inflammatory effects of vicenin-2 may be due to the interaction with the CaMKKβ-AMPK-SIRT1 axis.
A Systems Biology Approach for Prioritizing ASD Genes in Large or Noisy Datasets
Authors: Remori Veronica , Bondi Heather , Airoldi Manuel , Pavinato Lisa , Borini Giulia , Carli Diana , Brusco Alfredo , Fasano Mauro
Published: February 2025

Autism spectrum disorder (ASD) is a complex multifactorial neurodevelopmental disorder. Despite extensive research involving genome-wide association studies, copy number variant (CNV) testing, and genome sequencing, the comprehensive genetic landscape remains incomplete. In this context, we developed a systems biology approach to prioritize genes associated with ASD and uncover potential new candidates. A Protein–Protein Interaction (PPI) network was generated from genes associated to ASD in a public database. Leveraging gene topological properties, particularly betweenness centrality, we prioritized genes and unveiled potential novel candidates (e.g., CDC5L, RYBP, and MEOX2). To test this approach, a list of genes within CNVs of unknown significance, identified through array comparative genomic hybridization analysis in 135 ASD patients, was mapped onto the PPI network. A prioritized gene list was obtained through ranking by betweenness centrality score. Intriguingly, by over-representation analysis, significant enrichments emerged in pathways not strictly linked to ASD, including ubiquitin-mediated proteolysis and cannabinoid receptor signaling, suggesting their potential perturbation in ASD. Our systems biology approach provides a promising strategy for identifying ASD risk genes, especially in large and noisy datasets, and contributes to a deeper understanding of the disorder’s complex genetic basis.
Rotenone Induces Parkinsonism with Constipation Symptoms in Mice by Disrupting the Gut Microecosystem, Inhibiting the PI3K-AKT Signaling Pathway and Gastrointestinal Motility
Authors: Liu Li , Zhao Yan , Yang Weixing , Fan Yuqin , Han Lixiang , Sheng Jun , Tian Yang , Gao Xiaoyu
Published: February 2025

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Constipation is a prodromal symptom of PD. It is important to investigate the pathogenesis of constipation symptoms in PD. Rotenone has been successfully used to establish PD animal models. However, the specific mechanism of rotenone-induced constipation symptoms is not well understood. In this work, we found that constipation symptoms appeared earlier than motor impairment in mice gavaged with a low dose of rotenone (30 mg/kg·BW). Rotenone not only caused loss of dopaminergic neurons and accumulation of α-synuclein, but also significantly reduced serum 5-HT levels and 5-HTR4 in the striatum and colon. The mRNA expression of aquaporins, gastrointestinal motility factors (c-Kit, Cx43, smMLCK and MLC-3) in mouse colon was also significantly regulated by rotenone. In addition, both colon and brain showed rotenone-induced inflammation and barrier dysfunction; the PI3K/AKT pathway in the substantia nigra and colon was also significantly inhibited by rotenone. Importantly, the structure, composition and function of the gut microbiota were also significantly altered by rotenone. Some specific taxa were closely associated with motor and constipation symptoms, inflammation, and gut and brain barrier status in PD mice. Akkermansia, Staphylococcus and Lachnospiraceae_UCG—006 may play a role in exacerbating constipation symptoms, whereas Acinetobacter, Lactobacillus, Bifidobacterium, Solibacillus and Eubacterium_xylanophilum_groups may be beneficial in stimulating gastrointestinal peristalsis, maintaining motor function and alleviating inflammation and barrier damage in mice. In conclusion, low-dose rotenone can cause parkinsonism with constipation symptoms in mice by disrupting the intestinal microecosystem and inhibiting the PI3K-AKT pathway and gastrointestinal motility.
Citrulline Plus Arginine Induces an Angiogenic Response and Increases Permeability in Retinal Endothelial Cells via Nitric Oxide Production
Authors: Warden Cassandra , Zubieta Daniella , Brantley Milam A.
Published: February 2025

We previously observed elevated plasma levels of citrulline and arginine in diabetic retinopathy patients compared to diabetic controls. We tested our hypothesis that citrulline plus arginine induces angiogenesis and increases permeability in retinal endothelial cells. Human retinal microvascular endothelial cells (HRMECs) were treated with citrulline, arginine, or citrulline + arginine, and angiogenesis was measured with cell proliferation, migration, and tube formation assays. Permeability was measured in HRMEC monolayers via trans-endothelial electrical resistance (TEER) and FITC-labeled dextran. We also measured arginase activity, arginase-1 and arginase-2 expression, protein expression and phosphorylation of endothelial nitric oxide synthase (eNOS), and nitric oxide (NO) production. Citrulline + arginine induced endothelial cell proliferation (p = 0.018), migration (p = 0.011), and tube formation (p = 0.0042). Citrulline + arginine also increased FITC-dextran flow-through (p = 1.5 × 10−5) and decreased TEER (p = 0.010). Citrulline + arginine had no effect on arginase activity, but it increased eNOS (p = 6.3 × 10−4) and phosphorylated eNOS (p = 0.029), as well as NO production (p = 0.025). Inhibiting eNOS prevented the increase in NO (p = 0.0092), inhibited citrulline + arginine-induced cell migration (p = 0.0080) and tube formation (p = 0.0092), and blocked citrulline + arginine-related alterations in FITC-dextran flow-through (p = 3.6 × 10−4) and TEER (p = 3.9 × 10−4). These data suggest that citrulline + arginine treatment induces angiogenesis and increases permeability in retinal endothelial cells by activating eNOS and increasing NO production.
Enhanced Pathogenic Consequences Induced by a Seven-Amino-Acid Extension in the G Protein of the HRSV BA9 Genotype
Authors: Wang Na , Song Jingjing , Cao Lei , Mao Naiying , Shi Yuqing , Jiang Jie , Zhu Wuyang , Zhang Yan
Published: February 2025

In a previous outbreak of the human respiratory syncytial virus (HRSV), we identified a variant strain of genotype BA9 with a seven-amino-acid extension (Q-R-L-Q-S-Y-A) at the C-terminus of the attachment protein (G). To assess the impact of this extension on the virulence of HRSV, two full-length infectious clones using the wild strain of genotype BA9 as a backbone, one containing the seven-amino-acid extension (rRSV BA9 WT), and the other deleting this extension (rRSV BA9 Δ7AA), were successfully rescued using a reverse genetics system. The biological properties and virulence of the two rescued viruses were then compared and analyzed in vitro and in vivo. Compared to the rRSV BA9 Δ7AA, the rRSV BA9 WT exhibited a larger plaque size and a more pronounced suppression of the host cell innate immune response in vitro (IFN-β levels: 154.33 pg/mL vs. 11.27 pg/mL). The rRSV BA9 WT demonstrated increased adaptability in mice, with a 10-fold higher lung viral load and a stronger inflammatory response following intranasal exposure. Our study primarily demonstrated that the C-terminal extension of the G protein of the HRSV can enhance viral virulence, underscoring the importance of virological surveillance in the prevention and treatment of severe HRSV-related disease.
Genome-Wide Identification, Expression, and Protein Interaction of GRAS Family Genes During Arbuscular Mycorrhizal Symbiosis in Poncirus trifoliata
Authors: Song Fang , Ji Chuanya , Wang Tingting , Zhang Zelu , Duan Yaoyuan , Yu Miao , Song Xin , Jiang Yingchun , He Ligang , Wang Zhijing , Ma Xiaofang , Zhang Yu , Pan Zhiyong , Wu Liming
Published: February 2025

Arbuscular mycorrhizal (AM) fungi establish mutualistic symbiosis with most land plants, facilitating mineral nutrient uptake in exchange for photosynthates. As one of the most commercially used rootstocks in citrus, Poncirus trifoliata heavily depends on AM fungi for nutrient absorption. The GRAS gene family plays essential roles in plant growth and development, signaling transduction, and responses to biotic and abiotic stresses. However, the identification and functional characterization of GRAS family genes in P. trifoliata remains largely unexplored. In this study, a comprehensive genome-wide analysis of PtGRAS family genes was conducted, including their identification, physicochemical properties, phylogenetic relationships, gene structures, conserved domains, chromosome localization, and collinear relationships. Additionally, the expression profiles and protein interaction of these genes under AM symbiosis were systematically investigated. As a result, 41 GRAS genes were identified in the P. trifoliata genome, and classified into nine distinct clades. Collinearity analysis revealed seven segmental duplications but no tandem duplications, suggesting that segmental duplication played a more important role in the expansion of the PtGRAS gene family compared to tandem duplication. Additionally, 18 PtGRAS genes were differentially expressed in response to AM symbiosis, including orthologs of RAD1, RAM1, and DELLA3 in P. trifoliata. Yeast two-hybrid (Y2H) screening further revealed that PtGRAS6 and PtGRAS20 interacted with both PtGRAS12 and PtGRAS18, respectively. The interactions were subsequently validated through bimolecular fluorescence complementation (BiFC) assays. These findings underscored the crucial role of GRAS genes in AM symbiosis in P. trifoliata, and provided valuable candidate genes for improving nutrient uptake and stress resistance in citrus rootstocks through molecular breeding approaches.
Modified Cortisol Circadian Rhythm: The Hidden Toll of Night-Shift Work
Authors: Andreadi Aikaterini , Andreadi Stella , Todaro Federica , Ippoliti Lorenzo , Bellia Alfonso , Magrini Andrea , Chrousos George P. , Lauro Davide
Published: February 2025

The circadian rhythm of cortisol, a key hormone essential for maintaining metabolic balance and stress homeostasis, is profoundly disrupted by night-shift work. This narrative review examines the physiological mechanisms underlying cortisol regulation, the effects of shift work on its circadian rhythm, the associated health risks, and potential mitigation strategies. Night-shift work alters the natural secretion pattern of cortisol, leading to dysregulation of the hypothalamic–pituitary–adrenal axis, which in turn can contribute to metabolic disorders, cardiovascular diseases, and impaired cognitive function. Understanding the physiological pathways mediating these changes is crucial for developing targeted interventions to mitigate the adverse effects of circadian misalignment. Potential strategies, such as controlled light exposure, strategic napping, and personalized scheduling, may help to stabilize cortisol rhythms and improve health outcomes. This review aims to provide insights that can guide future research and inform occupational health policies for night-shift workers by addressing these challenges.
Rapid Identification of Alien Chromosome Fragments and Tracing of Bioactive Compound Genes in Intergeneric Hybrid Offspring Between Brassica napus and Isatis indigotica Based on AMAC Method
Authors: Guo Yanhong , Han Yutian , Gao Jinxiang , Ge Xianhong , Luo Yanqing , Zhao Kaiqin , Li Genze , Zu Feng , Cheng Xiaomao
Published: February 2025

Distant hybridization between Brassica napus and related genera serves as an effective approach for rapeseed germplasm innovation. Isatis indigotica, a wild relative of Brassica, has emerged as a valuable genetic resource for rapeseed improvement due to its medicinal properties. This study employed anchor mapping of alien chromosomal fragment localization (AMAC) method to efficiently identify alien chromosomal fragments in the progeny derived from distant hybridization between I. indigotica and Brassica napus, ‘Songyou No. 1’. Based on the AMAC method, we developed 193,101 IP and SSR markers utilizing the I. indigotica reference genome (Woad-v1.0). Through Electronic-PCR analysis against the Brassica and I. indigotica pan-genome, 27,820 specific single-locus (SSL) IP and SSR markers were obtained. Subsequently, 205 pairs of IP primers and 50 pairs of SSR primers were synthesized randomly, among which 148 pairs of IP markers (72.20%) and 45 pairs of SSR markers (90%) were verified as SSL molecular markers for the I. indigotica genome with no amplification product in four Brassica crops. These 193 SSL markers enable precise identification of one complete I6 chromosome and three chromosomal fragments (I1:1.17 Mb, I5:2.61 Mb, I7:1.11 Mb) in ‘Songyou No. 1’. Furthermore, we traced 32 genes involved in bioactive compound biosynthesis within/near these alien segments in ‘Songyou No. 1’ and developed seven functional markers. This study not only validates the efficacy of SSL markers for detecting exogenous chromatin in intergeneric hybrids but also provides valuable insights for the precise identification and mapping of desired chromosomal fragments or genes embedded in the derivatives from distant hybridization and potential applications in marker-assisted breeding for medicinal plant via distant hybridization strategy between I. indigotica and Brassica crops.
Bitter Taste Receptors 38 and 46 Regulate Intestinal Peristalsis
Authors: Camillo Lara , Pollastro Federica , Talmon Maria , Fresu Luigia Grazia
Published: February 2025

Bitter taste receptors (TAS2Rs) are expressed in extraoral tissues, exerting several functions and generating a whole-body chemosensory and protective system. TAS2Rs expression has been observed in the gastrointestinal tract, although their role is poorly understood. This study aims to investigate the role of TAS2R38 and 46 in human intestinal smooth muscle cells (HISMCs) after activation with the specific bitter ligands phenylthiocarbamide and absinthin, respectively. We found that TAS2R38 and 46 activation by phenylthiocarbamide (PTC) and absinthin, respectively, induces a rapid membrane depolarization and increase of cytosolic calcium levels due to internal storage in the IP3 pathway, resulting in an accelerated cell contraction. Overall, this study unravels, for the first time, the contractile impact of these TAS2R subtypes on intestinal smooth muscle cells, suggesting their involvement in gut peristalsis and recommending these receptors as possible targets for new therapies.
Proximity Effect of Optically Active h-BCN Nanoflakes Deposited on Different Substrates to Tailor Electronic, Spintronic, and Optoelectronic Properties
Authors: Alsaad Ahmad , Bai Jaeil , Mei Wai-Ning , Turallo Joel , Ilie Carolina , Sabirianov Renat
Published: February 2025

Hexagonal BCN (h-BCN), an isoelectronic counterpart to graphene, exhibits chirality and offers the distinct advantage of optical activity in the vacuum ultraviolet (VUV) region, characterized by significantly higher wavelengths compared to graphene nanoflakes. h-BCN possesses a wide bandgap and demonstrates desirable semiconducting properties. In this study, we employ Density Functional Theory (DFT) calculations to investigate the proximity effects of adsorbed h-BCN flakes on two-dimensional (2D) substrates. The chosen substrates encompass monolayers of 3D transition metals and WSe2, as well as a bilayer consisting of WSe2/Ni. Notably, the hydrogen-terminated h-BCN nanoflakes retain their planar configuration following adsorption. We observe a strong interaction between h-BCN and fcc-based monolayers such as Ni(111), resulting in the closure of the optical bandgap, while the adsorption energy on WSe2 is significantly weaker, preserving an approximate 1.1 eV bandgap. Furthermore, we demonstrate the magnetism induced by the proximity of adsorbed chiral h-BCN molecules, and the chiral-induced spin selectivity within the proposed systems.
SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders
Authors: Elazar Dana , Alvarez Natalie , Drobeck Sabrina , Gunn Teresa M.
Published: February 2025

The solute carrier family 1 member 4 (SLC1A4) gene encodes a neutral amino acid transporter, also referred to as alanine-serine-cysteine transporter 1, ASCT1, that helps maintain amino acid balance in the brain and periphery. In the brain, SLC1A4 plays an important role in transporting levo (L) and dopa (D) isomers of serine. L-serine is required for many cellular processes, including protein and sphingolipid synthesis, while D-serine is a co-agonist required for normal neurotransmission through N-methyl-D-aspartate receptors. Through its roles transporting L-serine across the blood–brain barrier and regulating synaptic D-serine levels, SLC1A4 helps establish and maintain brain health across the lifespan. This review examines the role of SLC1A4 in neurodevelopment and neurodegeneration and assesses the therapeutic potential of serine supplementation to treat neurodevelopmental symptoms associated with mutations in SLC1A4, as well as schizophrenia, depression, traumatic brain injury, and Alzheimer’s and Parkinson’s diseases.
FPGA Implementation of Multilayer Perceptron for Real-Time Detection of Power Quality Disturbances for Electric Vehicle Charger
Authors: Gaona-Cárdenas Luis-Fernando , Vazquez Nimrod , Estrada Leonel , Zamiri Elyas , de Castro Angel , Pinto Sergio
Published: February 2025

Power quality is one of the most critical fields in the energy sector. The connection of electric vehicles to the electrical grid can cause a degradation of energy quality when charging or discharging the battery. Identifying sudden voltage drops, surges, and network interruptions is essential to avoid network failure. A multiple fault classification/monitoring system has been developed based on artificial neural networks and implemented in an FPGA. The system’s performance has been evaluated using a set of data obtained from MATLAB/Simulink 2024. Different dataset combinations are implemented, trained, validated, and tested on three multilayer perceptron (MLP) models of various configurations. The analysis shows that the MLP designed with 12-bit fixed-point data precision is the most efficient MLP implementation in classification accuracy, compared to 8, 12, 20, and 24-bit fixed-point data. The system achieved 99.95% classification accuracy across various fault conditions, demonstrating its capability for real-time deployment.
Exercise Training and Cardiac Rehabilitation in Patients After Percutaneous Coronary Intervention: Comprehensive Assessment and Prescription
Authors: Adam Cristina Andreea , Erskine John , Akinci Buket , Kambic Tim , Conte Edoardo , Manno Girolamo , Halasz Geza , Sileikiene Vaida , Fogacci Federica , Perone Francesco
Published: February 2025

Current guidelines on acute and chronic coronary syndromes recommend comprehensive and multidisciplinary exercise-based cardiac rehabilitation in Class I. Indeed, in patients after a percutaneous coronary intervention, this supervised and structured rehabilitation program improves cardiovascular risk and reduces adverse events and mortality. After an initial assessment, including a peak exercise capacity evaluation, patients follow a tailored multidisciplinary program consisting of aerobic and resistance exercise training, risk factor management, dietary counselling, physical activity counselling, weight control management, psychosocial support, and education. However, tailored management and exercise prescription require careful assessment and risk consideration of several variables such as left ventricular dysfunction, comorbidities, aging, coronary artery disease severity, physical activity capacity, and type of coronary syndrome. The functional and prognostic benefits of cardiac rehabilitation have been widely demonstrated in patients after a percutaneous coronary intervention; however, referral is still limited, although exercise should be strongly recommended to these patients in the context of cardiovascular prevention. Therefore, the aim of our article is to provide an updated, critical, and state-of-the-art review of exercise training and cardiac rehabilitation programs in patients after a percutaneous coronary intervention. Furthermore, practical approaches to the management of these patients with a multidisciplinary and personalized intervention will be provided.
Corneal Graft Dehiscence in Patients on Oral Angiotensin-Inhibiting Medications: Plausible Relationship and Review of the Literature
Authors: Zhang Jie , Meyer Jay J
Published: February 2025

Wound dehiscence is a rare complication after penetrating keratoplasty (PK) that may occur with or without prior trauma. Multiple factors may influence corneal wound healing, including patient factors, corneal wound characteristics, and other external factors. There is also the possibility that systemic medications could impact corneal wound healing. Possible factors that may predispose a cornea to experience wound dehiscence are discussed. We propose a hypothesis that oral angiotensin-inhibiting medications could play a role in reduced corneal wound healing. A literature review was conducted to investigate the effect of angiotensin inhibitors on corneal wound healing. Five patients on systemic oral angiotensin-inhibiting medications at the time of PK developed dehiscence of the graft–host wound junction following removal of sutures. The dehiscence required resuturing in all cases and resulted in an expulsive choroidal hemorrhage and complete loss of vision in one eye. Age, diabetes, lack of corneal neovascularization, early suture removal, underlying epithelial basement membrane dystrophy, corneal oedema, slower tapering of topical corticosteroid dosage, and glaucoma medication with preservatives were possible predisposing factors for some of these instances of wound dehiscence. However, oral angiotensin-inhibiting medications were taken by all patients in this series, and the literature suggests that ACE inhibitors and ARBs can reduce corneal fibrosis, resulting in inadequate healing. Oral angiotensin-inhibiting medications could have played an anti-fibrotic role in these corneae and predisposed them to wound dehiscence with minimal trauma. Despite limited evidence, these medications warrant further investigation as potential modulators of corneal wound healing.
Expanding JETA’s Scope: Integrating AI-Driven Analytical Approaches
Authors: Rossi Marco
Published: February 2025

The landscape of experimental and theoretical analysis is evolving rapidly, driven by advancements in computational methods, data analytics, and artificial intelligence (AI) [...]