bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding Heritable Variation Among Hosts in Infectious Diseases Through the Lens of Twin Studies
Authors: Smatti Maria K. , Yassine Hadi M. , Mbarek Hamdi , Boomsma Dorret I.
Published: February 2025

Genetic factors have been hypothesized to contribute to the heterogeneity in the response to infectious diseases (IDs). The classical twin design provides a powerful tool to estimate the role of genetic contributions to variation in infection outcomes. With this design, the impact of heritability on the proneness as well as infection- and vaccine-induced immune responses have been documented for multiple infections, including tuberculosis, malaria, leprosy, otitis media, polio, mumps, measles, rubella, influenza, hepatitis B, and human papillomavirus infections, and recently, SARS-CoV-2. The current data show the heritable aspect in nearly all infections considered. In this contribution, we review and discuss human twin studies on the heritability of host characteristics in liability and response to IDs. This review emphasizes the importance of considering factors such as sex, disease stages, and disease presentation when assessing heritability and argues that the classical twin design provides a unique circumstance for exploring the genetic contribution as twins share levels of maternal antibodies, ancestral background, often the dates and number of vaccine doses, differences in vaccines’ manufacturing and storage, age, family environment, and other exposures. Additionally, we highlight the value of twin studies and the usefulness of combining the twin model with contemporary genomics technologies and advanced statistical tools to grasp a comprehensive and nuanced understanding of heritability in IDs.
Genetic Diversity Analysis and Comprehensive Evaluation of “M82” in EMS-Mutagenized Tomato
Authors: Yang Yanchao , Tan Zhanming , Liang Shuang , Cheng Wei , Sun Yihuan , Cheng Yunxia , Song Yu , Wang Yongming , Wu Jialong , Wang Qi
Published: February 2025

Background: Ethyl methyl sulfonate (EMS) mutagenesis is widely used because of its advantages of inducing point mutations and no need for genetic transformation. To identify germplasm resources of processed tomatoes with superior comprehensive traits suitable for cultivation in Xinjiang. Methods: In this study, tomato seeds were treated with 2% EMS reagent for 12 h, 21 quality traits and 20 quantitative traits of 33 processed tomatoes derived from EMS-mutagenized“M82”were evaluated. Results: The results indicated that for traits such as hypocotyl color, growth habit, plant type, leaf type, and leaf shape, the range of quantitative trait variation was 8.45–37.25%, with a genetic diversity index ranging from 1.25 to 2.07. Conclusions: Cluster analysis of quantitative traits categorized the 33 EMS-mutagenized “M82” processed tomato resources into five groups: Group I contained 22 robust germplasm samples; Group II consisted of a single potential high-quality germplasm; Group III comprised five germplasm with a small and extreme plant type; Group IV included four high-yield germplasm; and Group V represented one moderate, conventional germplasm. Raw data from 15 quantitative traits across the 33 accessions were standardized using the “extreme method” to extract six comprehensive factors. The top 10 germplasm resources based on the comprehensive score were 76, 137, 97, 102, 19, 104, 21, 108, 17, and 147. It provides some theoretical basis for realizing the high-yield and high-quality cultivation and variety breeding of processed tomatoes in Xinjiang.
Transcriptome Analysis Reveals Equine Endometrium’s Gene Expression Profile Around Embryo Fixation
Authors: Ulaangerel Tseweendolmaa , Mu Siqin , Sodyelalt Jolanqiqige , Yi Minna , Zhao Bilig , Hao Asiya , Wen Xin , Han Baoxiang , Bou Gerelchimeg
Published: February 2025

Background/Objectives: The success or failure of embryo fixation is crucial for embryo attachment and later development. As an epithelial chorioallantoic placenta-type animal, the horse has a special process of embryo implantation, and the mechanism of embryo fixation in horses is still unclear. Methods: In this study, the structural and transcriptomic characteristics of endometrial tissue from the fixed and nonfixed sides of 20-day gestation embryos in Mongolian horses were investigated to search for important genes and potential molecular markers associated with the fixation phase of equine embryos. Results: A comparison of the structures of the endometrial tissues of the two sides revealed that the endometrium on the fixed side presented distinctive features, which were characterized mainly by the development of glands on the fixed side compared with those on the nonfixed side. A total of 3987 differentially expressed genes were identified in the transcriptome, among which 1931 genes were highly expressed on the fixed side of the embryo, including CDH1, DRA, DQB, CLND2, BOLA-DQB, CLDN10, PTGER2, and PTGFR. The differentially expressed genes were enriched in biological processes such as cell adhesion, morphogenesis, NOD signaling, and vitamin uptake, as well as prostatic hormones. Conclusions: These results suggest that equine embryo fixation may depend at least on the regulation of prostaglandins and the establishment of cellular connections. This provides a foundation for exploring the molecular mechanisms of key genes and pathways related to equine embryo fixation and offers new insights into feeding management and the monitoring of mares in the early stages of pregnancy.
MLH1 Methylation Status and Microsatellite Instability in Patients with Colorectal Cancer
Authors: Rico-Méndez Manuel Alejandro , Trujillo-Rojas Miguel Angel , Ayala-Madrigal María de la Luz , Hernández-Sandoval Jesús Arturo , González-Mercado Anahí , Gutiérrez-Angulo Melva , Romero-Quintana José Geovanni , Valenzuela-Pérez Jesús Alonso , Ramírez-Ramírez Ruth , Flores-López Beatriz Armida , Moreno-Ortiz José Miguel
Published: February 2025

Background/Objectives: The purpose of the current study was to compare the methylation of five regions of the CpG island of MLH1 with the presence of microsatellite instability (MSI) in colorectal cancer (CRC) patients. Methods: The study analyzed 138 CRC tumor samples. DNA extraction was performed, followed by bisulfite conversion. MLH1 gene methylation was assessed by methylation-specific PCR (MS-PCR), and the resulting fragments were analyzed using polyacrylamide gels. MSI was evaluated using multiplex PCR, and the fragments were run through capillary electrophoresis. R studio (v4.4.1) and SPSS (v29.0) software were used for the statistical analysis, and values of p < 0.05 were considered statistically significant. Results: The study showed 75.4% unmethylated, 21% partially methylated, and 3.6% fully methylated samples, with region A frequently methylated. MSI was observed in 7.2% of cases (MSI-H: 5.8%, MSI-L: 1.4%). BAT-26 was the most unstable marker. A significant difference between MLH1 methylation and MSI-H (p < 0.01) was identified, but there was no relationship with specific MLH1 regions. Conclusions: No differences were identified when analyzing specific methylation regions in relation to MSI. This study is the first to describe MSI frequency in Mexican patients regardless of age.
Molecular Markers Specific for the Pseudomonadaceae Genera Provide Novel and Reliable Means for the Identification of Other Pseudomonas Strains/spp. Related to These Genera
Authors: Rudra Bashudev , Gupta Radhey S.
Published: February 2025

Background/Objectives: Taxon-specific conserved signature indels (CSIs) exhibit a strong predictive ability of being found in other members of specific taxa/genera. Recently, multiple exclusively shared CSIs were identified for several newly described Pseudomonadaceae genera (viz. Aquipseudomonas, Atopomonas, Caenipseudomonas, Chryseomonas Ectopseudomonas, Geopseudomonas, Halopseudomonas, Metapseudomonas, Phytopseudomonas, Serpens, Stutzerimonas, Thiopseudomonas, and Zestomonas). This study examines the potential applications of these CSIs for identifying other Pseudomonas spp. (strains) related to these genera. Methods: This work utilized the AppIndels.com server, which uses information regarding the presence of known taxon-specific CSIs in a genome for predicting its taxonomic affiliation. For this purpose, sequence information for different CSIs specific for the Pseudomonadaceae species/genera were added to the server’s database. Results: The AppIndels server was used to predict the taxonomic affiliation of 1972 genomes of unclassified Pseudomonas spp. (strains/isolates). Based upon finding a significant number of CSIs matching a specific taxon, the AppIndels server made positive predictions regarding the taxonomic affiliation of 299 examined genomes into the following clades/genera: Pseudomonas sensu stricto clade (46), Pseudomonas aeruginosa (64), Ectopseudomonas (46), Chryseomonas (32), Stutzerimonas (31), Metapseudomonas (22), Aquipseudomonas (21), Phytopseudomonas (17), Halopseudomonas (9), Geopseudomonas (4), Thiopseudomonas (3), Serpens (2), and Caenipseudomonas and Zestomonas (1 each). Phylogenetic studies confirmed that the taxonomic predictions by the server were 100% accurate. Conclusions: Our results demonstrate that the CSIs specific for Pseudomonadaceae species/genera, in conjunction with the AppIndels server, provides a novel and useful tool for identifying other species/strains affiliated with these species/genera. Phylogenetic studies suggest that many examined Pseudomonas strains constitute novel species in the indicated genera.
Integrating Machine Learning-Based Approaches into the Design of ASO Therapies
Authors: Leckie Jamie , Yokota Toshifumi
Published: February 2025

Rare diseases impose a significant burden on affected individuals, caregivers, and healthcare systems worldwide. Developing effective therapeutics for these small patient populations presents substantial challenges. Antisense oligonucleotides (ASOs) have emerged as a promising therapeutic approach that targets the underlying genetic cause of disease at the RNA level. Several ASOs have gained FDA approval for the treatment of genetic conditions, including use in personalized N-of-1 trials. However, despite their potential, ASOs often exhibit limited clinical efficacy, and optimizing their design is a complex process influenced by numerous factors. Machine learning-based platforms, including eSkip-Finder and ASOptimizer, have been developed to address these challenges by predicting optimal ASO sequences and chemical modifications to enhance efficacy. eSkip-Finder focuses on exon-skipping applications, while ASOptimizer aims to optimize ASOs for RNA degradation. Preliminary in vitro results have demonstrated the promising predictive power of these platforms. However, limitations remain, including their generalizability to alternative targets and gaps in their consideration of all factors influencing ASO efficacy and safety. Continued advancements in machine learning models, alongside efforts to incorporate additional features affecting ASO efficacy and safety, hold significant promise for the field. These platforms have the potential to streamline ASO development, reduce associated costs, and improve clinical outcomes, positioning machine learning as a key tool in the future of ASO therapeutics.
The Use and Understanding of Mild Cognitive Impairment in Routine Specialist Care: A Survey Among German Memory Clinics
Authors: Benson Gloria S. , Bartels Claudia , Stamatis Feride , Belz Michael , Esselmann Hermann , Frölich Lutz , Hausner Lucrezia
Published: February 2025

Objectives: Mild cognitive impairment (MCI) is a heterogeneous clinical syndrome and is important for the diagnosis and management of Alzheimer’s disease (AD). With the expansion of biomarker-based diagnostics, the aim of this study is to clarify the current attitudes towards and the use of MCI, and MCI due to AD, in German memory clinics. Methods: An online survey (50 items) was performed in 2022 among specialized clinicians (N = 45) in German memory clinics to assess the use of MCI and biomarkers in current diagnosis and treatment. Attitudinal and frequency items were assessed with a five-point numeric scale (strongly disagree = 1 to completely agree = 5 and never = 1 to always = 5, respectively). Results: All respondents used MCI as a clinical diagnosis. The benefits of diagnosing MCI were labeling deficits as disease symptoms (M = 4.4, SD = 0.7), improving coping with symptoms (M = 4.1, SD = 0.9), and motivating risk reduction activities (M = 4.0, SD = 0.9). Overall, 37 respondents used specialized diagnostic criteria for MCI due to AD, and all had access to biomarker diagnostics. Patients with MCI due to AD received more frequent counseling on memory training (p < 0.001), other non-pharmacological treatments (p < 0.001), and antidementive drug treatment (p < 0.001) than patients with MCI of other etiologies. Acetylcholinesterase inhibitors were prescribed significantly more frequently to patients with MCI due to AD (p < 0.001) compared to other MCI patients. Conclusions: MCI is commonly used as a clinical diagnosis in German memory clinics. AD biomarker assessment is well established and influences patient counseling and treatment recommendations.
Eighteenth-Century Day Excursions: Finding Authority in the Narration of Brief Visits and “A Diversity of Objects”
Authors: Kinsley Zoë
Published: February 2025

This article argues that a focus on the day excursion as a particular form of journey, with its inherent limits in relation to scale, distance, and duration, enables us to bring recent critical thinking on microtravel as a form with “foundations in the depth or intensity of description” into dialogue with scholarship that has given sustained attention to modes of descriptive practice that were specific to eighteenth-century British literature and the narrative representation of interior domestic space. The three English travellers under consideration are John Loveday (1711–1789), Dorothy Richardson (1748–1819), and Caroline Lybbe Powys (1738–1817). All made numerous home tour journeys of different kinds but never published their records of their travelling in their lifetimes. All displayed sustained interest in interior description, whether that was for the purpose of antiquarian research, as was the case with Loveday, and to some extent, Richardson, or as a means of collecting, arranging, and performing domestic aesthetic sensibility, as in the writing of both Richardson and Powys. The small local journeys analysed here speak of privileged leisure: the accounts offer experimentation in the narration of journeys made within limits, but those limits are rarely of opportunity. Yet these young travellers still negotiate authority: in the practice of day excursioning, and in writing up those experiences, we see each traveller utilising this compact form to find opportunities for self-assertion, employing the formulaic structures of antiquarian record and country house catalogue in order to articulate an independent curatorial voice.
Evaluation of Social Media Addiction and Its Relationship with Anxiety and Academic Performance Among Medical and Non-Medical Students: A Cross-Sectional Study from Saudi Arabia
Authors: Abdulsalim Suhaj , Anaam Mohammed Saif , Farooqui Maryam , Alshammari Mohammed S. , Alfadly Saeed , Alolayan Jehad , Aljarallah Anas Ahmad , Alsahali Saud
Published: February 2025

Background: Social media (SM) use has become an integral aspect of daily life. Overutilization of SM can adversely impact an individual’s physical and emotional well-being, especially that of students. This study evaluated the potential impact of SM addiction on anxiety and academic performance among university students. Methods: A cross-sectional study was conducted among medical ad non-medical students at Qassim University during September 2022–April 2023 after obtaining the Ethics Committee’s permission. Raosoft was used for calculating the sample size, and participants were selected through convenience sampling. Both descriptive and inferential statistics were used to analyze and interpret the results, using SPSS version 25. Results: A total of 269 students participated in the study. The majority of them were male (52%), with a mean age of 22.28. The main purpose of SM usage was entertainment, followed by communication. More than 30% of them were using SM for 4–6 h per day, accessing SM 1–10 times in a day, with more than half of them feeling that they had SM addiction and that it was affecting their daily activities and sleep. The majority of them agreed that SM can be used for group discussion (78.1% vs. 71.6%) and knowledge sharing (93.7% vs. 90%). However, a statistically significant difference was observed about anxiety level between the two groups. A negative correlation was found between cumulative grade point average (CGPA) and anxiety level. Conclusion: The findings suggest that SM has both positive and negative effects on academic performance and social anxiety. Continuous education and motivation about wise use of SM is warranted among students by parents, university authorities, and policymakers.
Optimizing Microclonal Propagation of Red Currant Cultivars: The Role of Nutrient Media, Sterilizers, and LED Lighting in Plant Adaptation
Authors: Panfilova Olga , Ryago Nelli , Ondrasek Gabrijel , Knyazeva Inna V. , Kahramanoğlu Ibrahim , Vershinina Oksana , Tsoy Mikhail , Izmailov Andrey Yu , Dorokhov Alexey S.
Published: February 2025

This study focuses on refining in vitro propagation protocols for red currant cultivars of the Ribes genus and evaluating the role of LED lighting in the adaptation of microplants. The cultivars ‘Red Lake’, ‘Englische Grosse Weisse’, ‘Marmeladnitsa’, and ‘Podarok Leta’ were successfully introduced into in vitro culture during their dormancy phase using 0.1% HgCl2 as a sterilizing agent. The period of spring introduction is not very efficient in connection with the intensive development of saprophytic microflora and weak morphogenesis microplants. Using 0.01% C9H9HgNaO2S sterilizer resulted in a decrease in the necrosis percentage, but an increase in mold proportion. The preparation of the plants with 12% H2O2 was considered environmentally not effective enough to obtain a large number of healthy microplants. The use of 12% H2O2 resulted in increased necrosis rates by 24.76% compared to 0.01% C9H9HgNaO2S and 0.1% HgCl2 sterilizers. The variety specificity of Ribesia plants in terms of the content of MS and LF nutrient media components was determined by the survival rate of explants, the formation of additional micro-shoots, and the morphological development. The MS medium with the addition of 1 mg∙L−1 BAP decreased the percentage of mold and necrosis infection and provided a high percentage of viable plants with optimal growth and reproduction rate. In contrast, the LF medium with the same concentration of 6-BAP resulted in poor explant quality and leaf chlorosis at later stages. The study also investigated the effects of different LED light spectra on morphological and physiological traits. For ‘Red Lake’ and ‘Englische Grosse Weisse’, RWUV-A (625–740 nm) lighting enhanced biomass and chlorophyll (Chl a and Chl a + b) accumulation, while the White (W) spectrum benefited ‘Podarok Leta’. Conversely, the RW spectrum with minimal green and no ultraviolet light restricted growth and photosynthetic pigment accumulation across all cultivars, promoting compact plant structures. The RWUV-A lighting condition resulted in the highest NDVI values across all cultivars, indicating an improved physiological status and biomass accumulation. These findings underscore the importance of refining the microclonal reproduction protocols for Ribesia subgenus representatives, emphasizing the genotype-specific light modulation during the proliferation stage. The study highlights the utility of the MS medium and tailored light conditions in enhancing the effectiveness of propagation techniques for producing high-quality planting material.
Light Controls in the Regulation of Carotenoid Biosynthesis in Leafy Vegetables: A Review
Authors: Kim Chang-Kyu , Eom Seok-Hyun
Published: February 2025

Leafy vegetables are excellent dietary sources of carotenoids, offering various nutritional benefits to human health. With the growing interest in health, the enhancement of functional compounds in crops through environmental control is emerging as an important topic in the field of agricultural research. Light serves as a major environmental signal regulating carotenoid levels. Light-activated photoreceptor proteins initiate intracellular signaling pathways that regulate carotenoid metabolism in response to environmental changes. Recent studies have shown that blue and ultraviolet (UV) light wavelengths are particularly effective in accumulation of foliar carotenoids, as they trigger photo-oxidative stress while activating defense mechanisms to mitigate it. Light intensity and exposure time, as quantitative aspects of light, are also involved in carotenoid biosynthesis in a similar manner. However, although previous studies provide valuable insights into light-mediated carotenoid accumulation, the interplay of light parameters (e.g., spectrum, intensity, exposure) with crop species and growth stages remains unclear due to the lack of well-organized data. In this review, we summarize recent advanced information about light-mediated carotenoid biosynthesis in leafy vegetables and highlight an integrated experimental approach to explore optimal light conditions for maximizing carotenoid accumulation in commercial production systems.
Effect of Induced Polyploidy on Morphology, Antioxidant Activity, and Dissolved Sugars in Allium cepa L.
Authors: Abubakar Mujahid Ado , Gennadievna Novitskaya Elena , Mikhailovna Son Oksana , Mikhailovna Kim Ekaterina
Published: February 2025

The role of onion as the second most-consumed and cultivated vegetable around the world and its renowned qualities that lead it to be called the “queen of the kitchen” have positioned it as a vital source of nutritional and economic contributions around the world. Polyploidy serves as a groundbreaking innovation in plant breeding, improving the yield and vigor of plants. This study was conducted to determine the effects of applying different concentrations of colchicine to onion seedlings on their morphology, antioxidant activity, and dissolved sugars. The mutagen was applied to the onion seeds at three different concentrations (0.05, 0.1, and 0.2% w/v) for an exposure period of 24 h. A chromosomal analysis confirmed the induction of polyploidy, which led to the successful duplication of the chromosome number from diploid (2n = 16) to tetraploid (4n = 32). The control recorded a survival rate of 91.57%, while 83.33%, 3.33%, and 0.00% survival rates were recorded for seedlings treated with 0.05%, 0.1%, and 0.2% (w/v) concentrations of colchicine, respectively. Furthermore, the tetraploids showed significant differences in morphology, producing the tallest seedlings (reaching up to 73.6 cm tall) and the greatest average bulb diameter (of 5.64 cm) after 14 weeks. The tetraploids also showed significant differences in antioxidant activity and the amount of dissolved sugars, recording the highest DPPH scavenging percentage of 72.58% and refractive index of 1.369. Successful induction of polyploidy was achieved with the application of 0.05% (w/v) colchicine, which produced tetraploids that are morphologically and biochemically superior to other treated and control plants at a significance level of p < 0.05.
Refuse or Ritual Deposit? The Complexity of Wari Household Archaeology
Authors: Nash Donna J.
Published: February 2025

The excavation of residential areas is a growing focus of research in Andean archaeology. Studies reveal that interpreting household remains from some prehispanic societies can be complex because of the nature of abandonment ritual, which may involve burnt offerings, the placement of valuables on floors, or the purposeful destruction of ceramic vessels that are distributed in patterned ways. The goods that constitute these offering practices can be confused with post-occupation refuse, especially when excavation units are relatively small. In this paper, I discuss the importance of assessing site formation processes in residential spaces and illustrate how different modes of household abandonment can make comparative analysis a complex exercise. I describe and compare several examples from Wari-affiliated residences at the sites of Cerro Baúl and Cerro Mejía, located in the department of Moquegua, Peru, to show how ritual depositions corresponding to house abandonment might affect the interpretation of daily domestic life. In particular, I examine how ritual assemblages have been interpreted as evidence of feasting to support propositions regarding the Wari political economy. I advocate that archaeologists interested in domestic areas, lifeways, and the political economy engage in large-scale horizontal excavations to ensure they can correctly distinguish between the remains of quotidian practices, the goods associated with ritual depositions, and refuse resulting from feasting, which is best substantiated with features and facilities to host empowering events.
Interventions Addressing Health Literacy in Cancer Care: A Systematic Review of Reviews
Authors: Jeitani Celine , Van den Broucke Stephan , Leemans Charlotte
Published: February 2025

(1) Background: Interventions addressing the health literacy (HL) of people suffering from an illness such as cancer can improve the understanding of the illness and lead to better-adapted behaviors, regarding the participation in cancer screenings, adhering to the complex multimodal therapy, participating in cancer treatment, and self-managing everyday health. This study provides a review of systematic reviews that include intervention articles addressing the HL of patients, healthcare professionals, and/or organizations in cancer, to identify the factors related to their effectiveness, as well as the missing elements, in light of the recent developments in HL research and practice. (2) Methods: A literature search was performed in Embase, Pubmed, PsycINFO, and Science Direct. Existing published reviews of studies targeting the interventions in the oncology domain, and which explicitly mentioned HL as a factor/outcome, were included. (3) Results: One hundred and fifty-five studies were retrieved. Ten fit the criteria and were included in this review. (4) Conclusions: Most of the interventions addressing HL in people with cancer included the target patients’ information and communication skills through education. To keep the full scope of the concept, as investigated in the recent literature, clinical applications of HL in patients with cancer should also consider organizational HL.
Advancing AI-Driven Geospatial Analysis and Data Generation: Methods, Applications and Future Directions
Authors: Hochmair Hartwig , Juhász Levente , Li Hao
Published: February 2025

Recent years have witnessed a revolution of artificial intelligence (AI) technologies, highlighted by the rise of generative AI and geospatial artificial intelligence (GeoAI) [...]
Enhancing Spatial Awareness and Collaboration: A Guide to VR-Ready Survey Data Transformation
Authors: McDuff Joseph Kevin , Karimi Armin Agha , Gharineiat Zahra
Published: February 2025

Surveying and spatial science are experiencing a paradigm shift from traditional data outputs to more immersive and interactive formats, driven by the rise in Virtual Reality (VR). This study addresses the challenge of transforming UAV (Unmanned Aerial Vehicle)-acquired photogrammetry data into VR-compatible surfaces while preserving the accuracy and quality crucial to professional surveying. The study leverages Blender, an open-source 3D creation tool, to develop a procedural guide for creating VR-ready models from high-quality survey data. The case study focuses on silos located in Yelarbon, Southeast Queensland, Australia. UAV mapping is utilised to gather the data necessary for 3D modelling with a few minor alterations in the photo capturing angle and processing. Key findings reveal that while Blender excels as a visualisation tool, it struggles with geospatial precision, particularly when handling large numbers coming from coordinate systems, leading to rounding errors seen within the VR model. Blender’s strength lies in creating immersive experiences for public engagement but is constrained by its lack of capability to hold survey metadata, hindering its applicability for professional survey-grade outputs. The results highlight the need for further development into possible Blender plugins that integrate geospatial accuracy with VR outputs. This study underscores the potential of VR to enhance how survey data are visualised, offering opportunities for future innovations in both the technical and creative aspects of the surveying profession.
Integrated Transcriptomics and Metabolomics Analysis Reveals Convergent and Divergent Key Molecular Networks of Dominant Genic Male Sterility and Cytoplasmic Male Sterility in Cabbage
Authors: Zhang Nan , Kuang Linqian , Yang Limei , Wang Yong , Han Fengqing , Zhang Yangyong , Wang Shaohui , Lv Honghao , Ji Jialei
Published: February 2025

Cytoplasmic male sterility (CMS) and dominant genic male sterility (DGMS) both result in the inability to produce or release functional pollen, making them pivotal systems in the hybridization breeding programs of Brassica crops such as cabbage (B. oleracea var. capitata). However, the underling molecular mechanisms are still largely unexplored. This study integrated transcriptomic and metabolomic analyses of cabbage DGMS line, Ogura CMS line, and the maintainer line to uncover the molecular mechanisms underlying these sterility types. The joint analysis predominantly identified significantly enriched pathways, including carbohydrate metabolism, flavonoid biosynthesis, and phenylpropanoid pathways between the MS lines and the maintainer. Especially, the CMS line exhibited a broader range of metabolic perturbations, with a total of 3556 significantly differentially expressed genes (DEGs) and 439 differentially accumulated metabolites (DAMs) detected, particularly in the vitamin B6 metabolism pathway, which showed significant alterations. Given the differences in the inactivation period of microspores in CMS and DGMS lines, we found that DEGs unique to DGMS and maintainer line, such as BoGRPs and BoLTPs, primarily regulate fertility development before the unicellular stage. The DEGs shared between CMS_vs_maintainer and DGMS_vs_maintainer mainly govern microspore development after release from the tetrad, such as BoHXK1 and BoIDH. Additionally, the DEGs unique to CMS_vs_maintainer may contribute to other damage in floral organs beyond male fertility, potentially leading to severe bud abortion, such as BoPNPO. These findings provide a comprehensive framework for understanding the molecular mechanisms of male sterility and offer valuable insights into future breeding strategies in cruciferous vegetables.
Effect of Fenugreek Extract on Testosterone Propionate-Induced Benign Prostatic Hyperplasia
Authors: Lee Jeong Yoon , Bang Jiyoung , Kim Jinhak , Baek Kwang-Soo , Oh Dongchan , Lee Yoo-Hyun
Published: February 2025

Benign prostatic hyperplasia (BPH) is a noncancerous urinary disorder that is common in older adult men; however, its underlying mechanisms remain unclear. Fenugreek has some biological effects, including hyperglycemia regulation, immune response modulation, and anti-cancer properties; In this study, we investigated the ameliorative effects of fenugreek seed extract (Forceterone® [FCT]) in a testosterone propionate (TP)-induced BPH animal model and its mechanisms in BPH-1 human prostate epithelial cells. Sprague Dawley (SD) rats were injected subcutaneously with TP (3 mg/kg) for 8 weeks to induce BPH while FCT was administered orally at 25, 50, and 100 mg/kg. In addition, BPH-1 cells were used to evaluate the inhibitory effects on cell proliferation and examine inflammatory cytokine expression. Treating rats with FCT decreased prostate weight, dihydrotestosterone (DHT) level, and proliferating cell nuclear antigen (PCNA) expression in the prostate. Furthermore, it decreased androgen receptor (AR), 5α-reductase 2, B-cell lymphoma 2 (Bcl-2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and NF-κB expression in vitro and in vivo and increased Bcl-2-associated X protein (Bax) expression. FCT also inhibited cell proliferation dose dependently in BPH-1 cells. These findings showed the potential use of FCT as an alternative treatment for BPH.
SARS-CoV-2 Variants: Genetic Insights, Epidemiological Tracking, and Implications for Vaccine Strategies
Authors: Alhamlan Fatimah S. , Al-Qahtani Ahmed A.
Published: February 2025

The emergence of SARS-CoV-2 variants has significantly impacted the global response to the COVID-19 pandemic. This review examines the genetic diversity of SARS-CoV-2 variants, their roles in epidemiological tracking, and their influence on viral fitness. Variants of concern (VOCs) such as Alpha, Beta, Gamma, Delta, and Omicron have demonstrated increased transmissibility, altered pathogenicity, and potential resistance to neutralizing antibodies. Epidemiological tracking of these variants is crucial for understanding their spread, informing public health interventions, and guiding vaccine development. The review also explores how specific mutations in the spike protein and other genomic regions contribute to viral fitness, affecting replication efficiency, immune escape, and transmission dynamics. By integrating genomic surveillance data with epidemiological and clinical findings, this review provides a comprehensive overview of the ongoing evolution of SARS-CoV-2 and its implications for public health strategies and new vaccine development.
FCRL1 and BAFF mRNA Expression as Novel Diagnostic and Prognostic Biomarkers in Diffuse Large B-Cell Lymphoma: Expression Signatures Predict R-CHOP Therapy Response and Survival
Authors: Al-Amodi Hiba S. , Bedair Hanan M. , Gohar Suzy , Mohamed Dalia Abdel-Wahab , Abd El Gayed Eman M. , Nazih Mahmoud , Hassan Sahar Badr , Sawan Eman S. , Elmahdy Esraa Elsayed , Mosbeh Asmaa , Efat Alaa , Abdelsattar Shimaa
Published: February 2025

This study investigated the diagnostic, prognostic, and therapeutic significance of Fc receptor-like 1 (FCRL1) and B-cell activating factor (BAFF) mRNA expression in Egyptian patients with diffuse large B-cell lymphoma (DLBCL) undergoing the standard R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) using quantitative real-time PCR (RT-qPCR). The results demonstrated that FCRL1 and BAFF mRNA expression were significantly elevated in DLBCL patients compared to healthy controls. A strong positive correlation existed between BAFF and FCRL1 expression levels. Diagnostic performance assessed through combined ROC curve analysis revealed that BAFF, FCRL1, and lactate dehydrogenase (LDH) achieved perfect diagnostic accuracy (AUC = 1.0), demonstrating 100% sensitivity, specificity, and predictive values. Further prognostic analysis using COX regression identified elevated FCRL1 expression as the most significant predictor of poor clinical outcomes. Kaplan–Meier survival analysis reinforced this finding, with high FCRL1 expression showing significant associations with reduced overall survival (OS, p = 0.031) and progression-free survival (PFS, p = 0.038). The study underscores the potential utility of BAFF and FCRL1 mRNA as diagnostic markers for DLBCL, with FCRL1 emerging as a promising prognostic marker and potential therapeutic target enabling more tailored treatment approaches for DLBCL, the most common type of B-cell non-Hodgkin lymphoma, and patients receiving R-CHOP therapy.
Design of New Daunorubicin Derivatives with High Cytotoxic Potential
Authors: Kalashnikova Aleksandra A. , Toibazarova Altynkul B. , Artyushin Oleg I. , Anikina Lada V. , Globa Anastasiya A. , Klemenkova Zinaida S. , Andreev Maxim V. , Radchenko Eugene V. , Palyulin Vladimir A. , Aleksandrova Yulia R. , Syzdykbayev Marat I. , Appazov Nurbol O. , Chubarev Vladimir N. , Neganova Margarita E. , Brel Valery K.
Published: February 2025

Chemotherapy with anthracycline antibiotics is a common method of treating tumors of various etiologies. To create more highly effective cytostatics based on daunorubicin, we used the method of reductive amination using polyalkoxybenzaldehydes. The obtained derivatives of the anthracycline structure have much greater cytotoxicity compared to daunorubicin due to increased affinity for DNA, the ability to disrupt the cell cycle, and their inhibition of the glycolysis process, which is confirmed by data from extensive biological studies and the results of molecular modeling.
miR-30d Levels Predict Re-Hospitalization in Patients with Acute Cardiogenic Pulmonary Edema: A Preliminary Study
Authors: Bianchi Giordano , Vizio Barbara , Bosco Ornella , Schiavello Martina , Cagna Vallino Paolo , Rumbolo Francesca , Morello Fulvio , Mengozzi Giulio , Montrucchio Giuseppe , Lupia Enrico , Pivetta Emanuele
Published: February 2025

Acute cardiogenic pulmonary edema (ACPE) is a common and serious manifestation of heart failure (HF), representing 10–20% of all acute HF admissions. It is associated with elevated in-hospital mortality and high rates of re-hospitalization. MicroRs, like miR-30d, are of particular interest in heart failure due to their regulatory role in gene expression and potential as biomarkers for diagnosing and predicting patient outcomes, especially in high-risk cases such as ACPE. We conducted a cohort study on patients diagnosed with ACPE in the Emergency Department (ED). The circulating levels of miR-30d were analyzed at the time of hospital admission and at one-month follow-up along with other biomarkers. We enrolled 24 ACPE patients and 10 control subjects. Median age was 80.8 years (interquartile range, IQR, 8.2) in ACPE cases, and 78.5 years (IQR 9.8) in controls with a male/female ratio of 2 and 0.66, respectively. In ACPE patients, median cardiac ejection fraction was 42.5%, creatinine 1.63 mg/dL (IQR 1.24), troponin 63.5 ng/dL (58), and NT-proBNP 4243.5 pg/mL (IQR 5846) at ED evaluation. Median concentration of miR30d was 0.81 in controls, and 3.67 and 7.28 in ACPE patients at enrollment time and one month later, respectively. Re-hospitalization occurred in 7 ACPE patients in the following 3 months, and in 9 during the following year. miR-30d had a significant predictive value in assessing the risk of re-hospitalization at both 3 months and 1 year following the initial diagnosis of ACPE, while it did not in assessing the risk of death at 1 year. When compared with the other biomarkers, none of them showed a better accuracy than miR-30d. Our findings suggest that elevated levels of miR-30d are associated with an increased rate of hospital readmission at both 3 months and 1 year after discharge. Larger, multicenter studies will be needed to confirm the validity of circulating miR-30d levels as a potential biomarker useful for risk prediction in ACPE patients and its utility in improving individualized patient care.
Connexin 43 Affects Pulmonary Artery Reactivity via Changes in Nitric Oxide Production and Influences Proliferative and Migratory Responses in Mouse Pulmonary Artery Fibroblasts
Authors: Wali Saad , Hwej Abdmajid , Welsh David J. , Wilson Kathryn , Kennedy Simon , Dempsie Yvonne
Published: February 2025

Pulmonary hypertension (PH) is a complex condition characterized by pulmonary artery constriction and vascular remodeling. Connexin 43 (Cx43), involved in cellular communication, may play a role in PH development. Cx43 heterozygous (Cx43+/−) mice show partial protection against hypoxia-induced pulmonary remodeling, with prior research highlighting its role in rat pulmonary artery fibroblast (PAF) proliferation and migration. However, inhibiting Cx43 may compromise nitric oxide (NO)-mediated vascular relaxation. This study evaluated the effects of Cx43 on mouse PAF (MPAF) proliferation, migration, NO-dependent and independent pulmonary vascular relaxation, and NO synthesis. Proliferation and migration were assessed in Cx43+/− MPAFs under normoxic and hypoxic conditions. Vascular responses were analyzed in intra-lobar pulmonary artery rings with acetylcholine (ACh), SNAP, and U46619, while NO production was measured in lung tissue. Both genetic knockdown and pharmacological inhibition of Cx43 significantly reduced serum-induced proliferation but not migration under normoxia, while 37,43Gap27 inhibited hypoxia-induced proliferation and migration. The effects of genetic knockdown and pharmacological inhibition of Cx43 on vascular reactivity were also investigated. NO-dependent and independent relaxations and NO production were reduced in Cx43+/− mice by 37,43Gap27. In conclusion, while Cx43 inhibition may protect against PAF proliferation and migration, it could also impair pulmonary vascular relaxation, at least in part through a reduction in NO signaling. Further studies are needed to fully understand the mechanisms by which Cx43 influences NO signaling.
Exertional Exhaustion (Post-Exertional Malaise, PEM) Evaluated by the Effects of Exercise on Cerebrospinal Fluid Metabolomics–Lipidomics and Serine Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Baraniuk James N.
Published: February 2025

Post-exertional malaise (PEM) is a defining condition of myalgic encephalomyelitis (ME/CFS). The concept requires that a provocation causes disabling limitation of cognitive and functional effort (“fatigue”) that does not respond to rest. Cerebrospinal fluid was examined as a proxy for brain metabolite and lipid flux and to provide objective evidence of pathophysiological dysfunction. Two cohorts of ME/CFS and sedentary control subjects had lumbar punctures at baseline (non-exercise) or after submaximal exercise (post-exercise). Cerebrospinal fluid metabolites and lipids were quantified by targeted Biocrates mass spectrometry methods. Significant differences between ME/CFS and control, non-exercise vs. post-exercise, and by gender were examined by multivariate general linear regression and Bayesian regression methods. Differences were found at baseline between ME/CFS and control groups indicating disease-related pathologies, and between non-exercise and post-exercise groups implicating PEM-related pathologies. A new, novel finding was elevated serine and its derivatives sarcosine and phospholipids with a decrease in 5-methyltetrahydrofolate (5MTHF), which suggests general dysfunction of folate and one-carbon metabolism in ME/CFS. Exercise led to consumption of lipids in ME/CFS and controls while metabolites were consumed in ME/CFS but generated in controls. In general, the frequentist and Bayesian analyses generated complementary but not identical sets of analytes that matched the metabolic modules and pathway analysis. Cerebrospinal fluid is unique because it samples the choroid plexus, brain interstitial fluid, and cells of the brain parenchyma. The quantitative outcomes were placed into the context of the cell danger response hypothesis to explain shifts in serine and phospholipid synthesis; folate and one-carbon metabolism that affect sarcosine, creatine, purines, and thymidylate; aromatic and anaplerotic amino acids; glucose, TCA cycle, trans-aconitate, and coenzyme A in energy metabolism; and vitamin activities that may be altered by exertion. The metabolic and phospholipid profiles suggest the additional hypothesis that white matter dysfunction may contribute to the cognitive dysfunction in ME/CFS.
Microbiota Co-Metabolism Alterations Precede Changes in the Host Metabolism in the Early Stages of Diet-Induced MASLD in Wistar Rats
Authors: Martín-Grau María , Casanova Pilar , Moreno-Morcillo Laura , Morales José Manuel , Marrachelli Vannina G. , Monleón Daniel
Published: February 2025

Metabolic-dysfunction-associated steatotic liver disease (MASLD) affects around 30% of the global population. The sexual dimorphism and gut microbiota play an important role in the early development of MASLD. The main objective of this research was to investigate metabolic changes during the early subclinical MASLD progression, for identifying the sequence of events and evaluating the impact of sexual dimorphism and the microbiota on the initial stages of MASLD development. Male and female Wistar rats 18 weeks old were randomly divided into different groups and fed a chow diet or a 45% high-fat diet for 21 weeks. Every three weeks, samples of serum, urine, and faeces were collected and studied by metabolomics. Furthermore, the liver was analysed at the endpoint. In addition, the gut microbiota was analysed from faecal samples over time using 16S rRNA gene-targeted group-specific primers. Our results revealed that three weeks on an HFD reduced the bacterial diversity in the faecal microbiota of Wistar rats, accompanied by changes in the faecal and urine metabolome. The HFD-induced alterations in microbiota-related co-metabolites in the liver, blood, urine, and faeces indicate a significant role of host–microbiota co-metabolism changes in the early stages of MASLD. In this study, we provide a comprehensive longitudinal analysis, detailing the sequence of events in the early development of MASLD. Our findings suggest that alterations in the gut microbiota diversity and co-metabolism occur before changes in host metabolism in the early onset of liver steatosis, a subclinical phase of MASLD.
ZEB2 Gene Pathogenic Variants Across Protein-Coding Regions and Impact on Clinical Manifestations: A Review
Authors: Hossain Waheeda A. , St. Peter Caroline , Lovell Scott , Rafi Syed K. , Butler Merlin G.
Published: February 2025

Mowat–Wilson syndrome (MWS) is a rare multi-system genetic disorder caused by variants in the Zinc Finger E-Box-Binding Homeobox 2 (ZEB2) gene. ZEB2 is an autosomal dominant gene containing ten exons within the canonical version transcript (Isoform: O60315-1). The ZEB2 gene encodes six functional domains and seven non-domain regions. This review provides a comprehensive summary of pathogenic variants and their associated MWS clinical characteristics, focusing on ZEB2 pathogenic variants, functional protein domains and non-domain regions with clinical features. A systematic literature search from 2001 to 2023 and of unpublished datasets found 191 individuals with reported clinical features and genotypic data. Genetic defects and clinical manifestations were examined that presumably impact on the structure and function of the ZEB2 gene, thereby causing multiple developmental defects with corresponding clinical presentation. This study found more nonsense ZEB2 variants observed within exon 8, which encodes four of the six protein domains: the CtBP-interacting domain (CID), homeodomain (HD), SMAD-binding domain (SMD or SBD) and part of the N-terminal zinc finger cluster (N-ZF), suggesting exon 8 plays a crucial role in this protein structure and function with multi-organ involvement. Exon 8 defects were found to be statistically more represented for gastrointestinal findings when compared to other exons, while frameshift defects were more often seen for the typical MWS face in non-domain protein regions. In contrast, nonsense or other types of variants in exons 3, 4 and 5 which encode only flanking non-domain regions were observed more often, compared with other exons excluding exon 8, to be specifically involved in the MWS facial gestalt, brain malformations, developmental delay and intellectual disability. Deleterious ZEB2 frameshift (45%) and nonsense (38%) gene variants were most often observed with deletions at 6% and missense at 5%. The genotype and clinical relationships in MWS can provide insights into prognosis, morbidity, clinical surveillance strategies and counseling of family members.