bluuebunny/crossref_metadata_2025 huggingface dataset:
Demand Potential for Agricultural Trade between China and Countries along the “Belt and Road”
Authors: Zhou Lunzheng , Tong Guangji , Qi Jiaguo , He Lu
Published: October 2024

International agricultural markets are an important part of the global food resource chain. Tapping into the potential of agricultural trade between China and countries along the “Belt and Road” (B&R) is conducive to safeguarding China’s and the world’s food security, but there is less literature on the potential of bilateral trade demand. This paper ranks the B&R countries according to the scale of imports and exports, and calculates the elasticity of demand for imports, the elasticity of substitution for exports, and, finally, the potential of elasticity of demand for trade between China and the major B&R countries. The results show that China’s agricultural export potential to major B&R countries is ranked as follows: Indonesia, Thailand, Russia, Poland, Turkey, Vietnam, Malaysia, Ukraine, India, and Singapore. The major B&R countries are also ranked in terms of their export potential to China: Vietnam, India, Ukraine, Russia, Malaysia, Thailand, Indonesia, Poland, Singapore, and Turkey. The findings of this paper provide a decision-making basis for promoting agricultural trade between China and B&R countries.
Preparation of Cassia Bean Gum/Soy Protein Isolate Composite Matrix Emulsion Gel and Its Effect on the Stability of Meat Sausage
Authors: Zou Qiang , Zheng Yuhan , Liu Yudie , Luo Linghui , Chen Yuyou , Ran Guilian , Liu Dayu
Published: October 2024

The use of plant-derived emulsified gel systems as fat substitutes for meat products has always been an important direction in the development of healthy foods. In this study, a composite matrix emulsion gel was prepared with soy protein isolate (SPI) and different concentrations of cassia bean gum (CG), and then the selected emulsion gel was applied to meat sausage as a fat substitute to explore its stability. Our results showed that the hardness, chewiness, viscosity, shear stress, and G′ and G″ moduli of the emulsion gel increased considerably with the cassia bean gum concentration, the thickness of the emulsion gel increased, and the pore size decreased. The gel strength of the 1.75% CG/SPI emulsion gel was the highest, which was 586.91 g. The elasticity was 0.94 mm, the masticability was 452.94 mJ, and the water-holding capacity (WHC) was 98.45%. Then, the 1.75% CG/SPI emulsion gel obtained via screening was applied as a fat substitute in meat sausage. With an increase in the substitution amount, the cooking loss, emulsification stability, pH, color difference, texture, and antioxidant activity of the meat sausage before and after freezing and thawing increased first and then decreased. The indexes of meat sausage with 50% fat replacement were not considerably different from those of full-fat meat sausage. This study can provide a theoretical basis for the application of plant-derived emulsified gel systems as fat substitutes in meat sausage.
Genome-Wide Characterization and Expression Profiling of Phytosulfokine Receptor Genes (PSKRs) in Triticum aestivum with Docking Simulations of Their Interactions with Phytosulfokine (PSK): A Bioinformatics Study
Authors: Khalil Hala Badr
Published: October 2024

Background/Objectives: The phytosulfokine receptor (PSKR) gene family plays a crucial role in regulating plant growth, development, and stress response. Here, the PSKR gene family was characterized in Triticum aestivum L. The study aimed to bridge knowledge gaps and clarify the functional roles of TaPSKRs to create a solid foundation for examining the structure, functions, and regulatory aspects. Methods: The investigation involved genome-wide identification of PSKRs through collection and chromosomal assignment, followed by phylogenetic analysis and gene expression profiling. Additionally, interactions with their interactors were stimulated and analyzed to elucidate their function. Results: The wide-genome inspection of all TaPSKRs led to 25 genes with various homeologs, resulting in 57 TaPSKR members distributed among the A, B, and D subgenomes. Investigating the expression of 61 TaPSKR cDNAs in RNA-seq datasets generated from different growth stages at 14, 21, and 60 days old and diverse tissues such as leaves, shoots, and roots provided further insight into their functional purposes. The expression profile of the TaPSKRs resulted in three key clusters. Gene cluster 1 (GC 1) is partially associated with root growth, suggesting that specific TaPSKRs control root development. The GC 2 cluster targeted genes that show high levels of expression in all tested leaf growth stages and the early developmental stage of the shoots and roots. Furthermore, the GC 3 cluster was composed of genes that are constantly expressed, highlighting their crucial role in regulating various processes during the entire life cycle of wheat. Molecular docking simulations showed that phytosulfokine type α (PSK-α) interacted with all TaPSKRs and had a strong binding affinity with certain TaPSKR proteins, encompassing TaPSKR1A, TaPSKR3B, and TaPSKR13A, that support their involvement in PSK signaling pathways. The crucial arbitration of the affinity may depend on interactions between wheat PSK-α and PSKRs, especially in the LRR domain region. Conclusions: These discoveries deepened our knowledge of the role of the TaPSKR gene family in wheat growth and development, opening up possibilities for further studies to enhance wheat durability and yield via focused innovation approaches.
Interprofessional In Situ Simulation’s Impact on Healthcare Personnel’s Competence and Reported Need for Training in Cardiopulmonary Resuscitation—A Pilot Study in Norway
Authors: Grasto Kristina , Leonardsen Ann-Chatrin Linqvist
Published: October 2024

Background/objectives: International guidelines recommend cardiopulmonary resuscitation [CPR] training every sixth month. However, research indicates that more training is needed to maintain CPR competence. The objectives of this pilot study were (a) to assess health personnel’s self-reported competence and need for more training in CPR before and after interprofessional in situ CPR simulation and (b) to assess time since the last CPR course and respondent’s reported need for more training. Also, we wanted a pilot to assess areas of improvement in a future, larger study. Methods: A questionnaire was administered to healthcare personnel in hospital wards receiving CPR training using a purposeful sampling strategy. Results: In total, 311 respondents answered the pre-intervention and 45 respondents answered the post-intervention survey. The respondents believed they had good knowledge, skills, and training in CPR, and about 2/3 of the respondents reported a need for more knowledge, skills, and training. There was a weak positive correlation between the time since the last CPR course and the perceived need for more training [p < 0.05]. There were no significant differences in self-reported competence or perceived need for more training pre- and post-intervention. The pilot detected several limitations that need improvement in a future study. Conclusions: The authors suggest that regular training is important for maintaining competence in CPR. Also, in a future study, comparisons at an individual level, as well as assessments by experts and of non-technical skills, should be included.
New Trichoderma Strains Suppress Blue Mold in Oranges by Damaging the Cell Membrane of Penicillium italicum and Enhancing Both Enzymatic and Non-Enzymatic Defense Mechanisms in Orange Fruits
Authors: El-Nagar Asmaa , Mazrou Yasser S. A. , El-Fawy Mansour M. , Abou-Shlell Mohamed K. , Seleim Mohamed A. A. , Makhlouf Abeer H. , Hegazy Mohamed G. A.
Published: October 2024

Blue mold disease, caused by Penicillium italicum (P. italicum), presents a significant challenge to orange fruits (Citrus sinensis L.) and other citrus crops globally. Biological control, particularly Trichoderma species, offers a promising alternative to synthetic fungicides. Therefore, this study aimed to isolate, identify, and evaluate the antagonistic activities of two Trichoderma isolates against P. italicum. These isolates were molecularly identified and assigned accession numbers PP002254 and PP002272, respectively. Both isolates demonstrated significant antifungal activity in dual culture assays. Moreover, the culture filtrates (CFs) of Trichoderma longibrachiatum PP002254 and Trichoderma harzianum PP002272 suppressed the mycelial growth of P. italicum by 77.22% and 71.66%, respectively. Additionally, CFs reduced the severity of blue mold on orange fruits by 26.85% and 53.81%, compared to 100% in the control group. Scanning electron microscopy revealed that treated P. italicum hyphae were shrunken and disfigured. Enzyme activities (catalase, peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase) in treated oranges increased, along with total soluble phenolics and flavonoids. Conversely, malondialdehyde (MDA) levels decreased in treated fruits. These findings suggest that T. longibrachiatum PP002254 and T. harzianum PP002272 could be effective biocontrol agents for managing blue mold and other citrus postharvest diseases.
Shading Impairs Mycorrhizal Benefits on Plant Growth, Leaf Gas Exchange, and Active Ingredients in Polygonum cuspidatum
Authors: Deng Ci , Zhang Ze-Zhi , da Silva Fábio Sérgio Barbosa , Hashem Abeer , Abd_Allah Elsayed Fathi , Zou Ying-Ning , Wu Qiang-Sheng
Published: October 2024

Polygonum cuspidatum, an important medicinal plant, often experiences shading from surrounding vegetation during its growth phase, raising questions about the impact of such conditions on the functionality of arbuscular mycorrhizal fungi. This study investigated the effects of an arbuscular mycorrhizal fungus (Funneliformis mosseae) on the growth, leaf gas exchange, and concentrations of active ingredient concentrations in leaves and roots of P. cuspidatum under shading (with a 72% shading rate) conditions. A nine-week shading intervention significantly suppressed root colonization by F. mosseae and the formation of soil mycorrhizal mycelium. Shading significantly inhibited the above-ground growth performance, biomass production, leaf photosynthetic rate, transpiration rate, stomatal conductance, and intercellular CO2 concentration, while F. mosseae significantly increased these variables in the absence of shading. Plant height, leaf biomass, stem biomass, leaf photosynthetic rate, transpiration rate, and stomatal conductance were all decreased by F. mosseae when the plants were shaded. The shading treatment also significantly diminished the concentrations of active components measured in both leaves and roots. Under no-shading conditions, F. mosseae significantly boosted the concentrations of polydatin, resveratrol, aloe-emodin, emodin, chrysophanol, and physcion in roots, as well as the concentrations of polydatin and chrysophanol in leaves. Conversely, in the presence of shading, F. mosseae distinctly reduced these active ingredient levels in roots, followed by an increase in leaf polydatin and chrysophanol concentrations. In summary, shading substantially impaired the mycorrhizal benefits on plant growth, leaf gas exchange, and root active ingredients in P. cuspidatum, highlighting the importance of sufficient light to maximize mycorrhizal contributions.
Using the Social–Ecological Model to Assess Vaccine Hesitancy and Refusal in a Highly Religious Lower–Middle-Income Country
Authors: Chait Rachael M. , Nastiti Anindrya , Chintana Delfi Adlina , Sari Putri Nilam , Marasabessy Nabila , Firdaus Muhamad Iqbal , Dirgawati Mila , Agustian Dwi , West Heidi , Ariesyady Herto Dwi , Shibata Tomoyuki
Published: October 2024

(1) Background: The aim of this study was to understand the factors associated with vaccine hesitancy and refusal in Indonesia using the Social–Ecological Model (SEM). (2) Methods: Data on demographics, religiosity, family dynamics, and perceptions of public health efforts were collected through an online survey and compared to the rates of vaccine hesitancy and refusal. (3) Results: Income and sex were significantly associated with vaccine hesitancy. Based on a vaccine passport policy to enter public spaces, people who felt inhibited to enter public spaces or perceived privacy threats were twice as likely to exhibit vaccine hesitancy. Participants who believed that religious groups had a difficult time getting vaccinated were nearly twice as likely to exhibit vaccine hesitancy and three times more likely to exhibit vaccine refusal. However, participants who believed in a higher religious power were 58% less likely to exhibit vaccine hesitancy. Religious leaders significantly influenced participants to make the decision regarding vaccination. Individuals with vaccine refusal were more than twice as likely to share information with others without fact-checking. Notably, structural barriers such as distance and transportation were most strongly associated with vaccine hesitancy and refusal. (4) Conclusion: Cultural factors play a significant role in vaccine hesitancy and refusal. The SEM can be used to propose multi-level interventions with collaboration and communication among stakeholders to improve community health.
Genomics and Bioinformatics in One Health: Transdisciplinary Approaches for Health Promotion and Disease Prevention
Authors: Scarpa Fabio , Casu Marco
Published: October 2024

The One Health concept underscores the interconnectedness of human, animal, and environmental health, necessitating an integrated, transdisciplinary approach to tackle contemporary health challenges. This perspective paper explores the pivotal role of genomics and bioinformatics in advancing One Health initiatives. By leveraging genomic technologies and bioinformatics tools, researchers can decode complex biological data, enabling comprehensive insights into pathogen evolution, transmission dynamics, and host-pathogen interactions across species and environments (or ecosystems). These insights are crucial for predicting and mitigating zoonotic disease outbreaks, understanding antimicrobial resistance patterns, and developing targeted interventions for health promotion and disease prevention. Furthermore, integrating genomic data with environmental and epidemiological information enhances the precision of public health responses. Here we discuss case studies demonstrating successful applications of genomics and bioinformatics in One Health contexts, such as including data integration, standardization, and ethical considerations in genomic research. By fostering collaboration among geneticists, bioinformaticians, epidemiologists, zoologists, and data scientists, the One Health approach can harness the full potential of genomics and bioinformatics to safeguard global health. This perspective underscores the necessity of continued investment in interdisciplinary education, research infrastructure, and policy frameworks to effectively employ these technologies in the service of a healthier planet.
Lepidium peruvianum as a Source of Compounds with Anticancer and Cosmetic Applications
Authors: Kasprzak Dorota , Gaweł-Bęben Katarzyna , Kukula-Koch Wirginia , Strzępek-Gomółka Marcelina , Wawruszak Anna , Woźniak Sylwia , Chrzanowska Marcelina , Czech Karolina , Borzyszkowska-Bukowska Julia , Głowniak Kazimierz , Matosiuk Dariusz , Orihuela-Campos Rita Cristina , Jodłowska-Jędrych Barbara , Laskowski Tomasz , Meissner Henry O.
Published: October 2024

Lepidium peruvianum—an edible herbaceous biennial plant distributed in the Andes—has been used for centuries as food and as a natural medicine in treating hormonal disorders, as an antidepressant, and as an anti-osteoporotic agent. The presented study aims to prove its beneficial cosmetic and chemopreventive properties by testing the antiradical, whitening, cytotoxic, and anticancer properties of differently colored phenotypes that were extracted using three solvents: methanol, water, and chloroform, with the help of the chemometric approach to provide evidence on the impact of single glucosinolanes (seven identified compounds in the HPLC-ESI-QTOF-MS/MS analysis) on the biological activity of the total extracts. The tested extracts exhibited moderate antiradical activity, with the methanolic extract from yellow and grey maca phenotypes scavenging 49.9 ± 8.96% and 48.8% ± 0.44% of DPPH radical solution at a concentration of 1 mg/mL, respectively. Grey maca was the most active tyrosinase inhibitor, with 72.86 ± 3.42% of the enzyme activity calculated for the water extract and 75.66 ± 6.21% for the chloroform extract. The studies in cells showed no cytotoxicity towards the human keratinocyte line HaCaT in all studied extracts and a marked inhibition of cell viability towards the G361 melanoma cell line, which the presence of pent-4-enylglucosinolate, glucotropaeolin, and glucoalyssin in the samples could have caused. Given all biological activity tests combined, the three mentioned compounds were shown to be the most significant positive contributors to the results obtained, and the grey maca water extract was found to be the best source of the former compound among the tested samples.
CRISPR/Cas9-Mediated fech Knockout Zebrafish: Unraveling the Pathogenesis of Erythropoietic Protoporphyria and Facilitating Drug Screening
Authors: Wijerathna Hitihami M. S. M. , Shanaka Kateepe A. S. N. , Raguvaran Sarithaa S. , Jayamali Bulumulle P. M. V. , Kim Seok-Hyung , Kim Myoung-Jin , Jung Sumi , Lee Jehee
Published: October 2024

Erythropoietic protoporphyria (EPP1) results in painful photosensitivity and severe liver damage in humans due to the accumulation of fluorescent protoporphyrin IX (PPIX). While zebrafish (Danio rerio) models for porphyria exist, the utility of ferrochelatase (fech) knockout zebrafish, which exhibit EPP, for therapeutic screening and biological studies remains unexplored. This study investigated the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated fech-knockout zebrafish larvae as a model of EPP1 for drug screening. CRISPR/Cas9 was employed to generate fech-knockout zebrafish larvae exhibiting morphological defects without lethality prior to 9 days post-fertilization (dpf). To assess the suitability of this model for drug screening, ursodeoxycholic acid (UDCA), a common treatment for cholestatic liver disease, was employed. This treatment significantly reduced PPIX fluorescence and enhanced bile-secretion-related gene expression (abcb11a and abcc2), indicating the release of PPIX. Acridine orange staining and quantitative reverse transcription polymerase chain reaction analysis of the bax/bcl2 ratio revealed apoptosis in fech−/− larvae, and this was reduced by UDCA treatment, indicating suppression of the intrinsic apoptosis pathway. Neutral red and Sudan black staining revealed increased macrophage and neutrophil production, potentially in response to PPIX-induced cell damage. UDCA treatment effectively reduced macrophage and neutrophil production, suggesting its potential to alleviate cell damage and liver injury in EPP1. In conclusion, CRISPR/Cas9-mediated fech−/− zebrafish larvae represent a promising model for screening drugs against EPP1.
Proof of Concept for Genome Profiling of the Neurofibroma/Sarcoma Sequence in Neurofibromatosis Type 1
Authors: Cannizzaro Ilenia Rita , Treccani Mirko , Taiani Antonietta , Ambrosini Enrico , Busciglio Sabrina , Cesarini Sofia , Luberto Anita , De Sensi Erika , Moschella Barbara , Gismondi Pierpacifico , Azzoni Cinzia , Bottarelli Lorena , Giordano Giovanna , Corradi Domenico , Silini Enrico Maria , Zanatta Valentina , Cennamo Federica , Bertolini Patrizia , Caggiati Patrizia , Martorana Davide , Uliana Vera , Percesepe Antonio , Barili Valeria
Published: October 2024

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder characterized by the predisposition to develop tumors such as malignant peripheral nerve sheath tumors (MPNSTs) which represents the primary cause of death for NF1-affected patients. Regardless of the high incidence and mortality, the molecular mechanisms underneath MPNST growth and metastatic progression remain poorly understood. In this proof-of-concept study, we performed somatic whole-exome sequencing (WES) to profile the genomic alterations in four samples from a patient with NF1-associated MPNST, consisting of a benign plexiform neurofibroma, a primary MPNST, and metastases from lung and skin tissues. By comparing genomic patterns, we identified a high level of variability across samples with distinctive genetic changes which allow for the definition of profiles of the early phase with respect to the late metastatic stages. Pathogenic and likely pathogenic variants were abundant in the primary tumor, whereas the metastatic samples exhibited a high level of copy-number variations (CNVs), highlighting a possible genomic instability in the late phases. The most known MPNST-related genes, such as TP53 and SUZ12, were identified in CNVs observed within the primary tumor. Pathway analysis of altered early genes in MPNST pointed to a potential role in cell motility, division and metabolism. Moreover, we employed survival analysis with the TCGA sarcoma genomic dataset on 262 affected patients, in order to corroborate the predictive significance of the identified early and metastatic MPNST driver genes. Specifically, the expression changes related to the mutated genes, such as in RBMX, PNPLA6 and AGAP2, were associated with reduced patient survival, distinguishing them as potential prognostic biomarkers. This study underlines the relevance of integrating genomic results with clinical information for early diagnosis and prognostic understanding of tumor aggressiveness.
From Cancer to Immune Organoids: Innovative Preclinical Models to Dissect the Crosstalk between Cancer Cells and the Tumor Microenvironment
Authors: Picca Francesca , Giannotta Claudia , Tao Jiahao , Giordanengo Lucia , Munir H. M. Waqas , Botta Virginia , Merlini Alessandra , Mogavero Andrea , Garbo Edoardo , Poletto Stefano , Bironzo Paolo , Doronzo Gabriella , Novello Silvia , Taulli Riccardo , Bersani Francesca
Published: October 2024

Genomic-oriented oncology has improved tumor classification, treatment options, and patient outcomes. However, genetic heterogeneity, tumor cell plasticity, and the ability of cancer cells to hijack the tumor microenvironment (TME) represent a major roadblock for cancer eradication. Recent biotechnological advances in organotypic cell cultures have revolutionized biomedical research, opening new avenues to explore the use of cancer organoids in functional precision oncology, especially when genomics alone is not a determinant. Here, we outline the potential and the limitations of tumor organoids in preclinical and translational studies with a particular focus on lung cancer pathogenesis, highlighting their relevance in predicting therapy response, evaluating treatment toxicity, and designing novel anticancer strategies. Furthermore, we describe innovative organotypic coculture systems to dissect the crosstalk with the TME and to test the efficacy of different immunotherapy approaches, including adoptive cell therapy. Finally, we discuss the potential clinical relevance of microfluidic mini-organ technology, capable of reproducing tumor vasculature and the dynamics of tumor initiation and progression, as well as immunomodulatory interactions among tumor organoids, cancer-associated fibroblasts (CAFs) and immune cells, paving the way for next-generation immune precision oncology.
The 9 bp Deletion between the Mitochondrial COII and Lysine tRNA Genes in a Caucasian Population with Cognitive Disorders: An Observational Study
Authors: Giuliano Marika , Santa Paola Sandro , Borgione Eugenia , Lo Giudice Mariangela , Di Blasi Francesco Domenico , Pettinato Rosa , Romano Corrado , Scuderi Carmela
Published: October 2024

The loss of one of the two copies of the 9 bp tandem repeat sequence (CCCCCTCTA) located in the small non-coding region between the cytochrome oxidase II (COII) and the lysine tRNA genes in human mtDNA has been reported to be polymorphic in Asian, Oceanian and Sub-Saharan African populations, but it has rarely been observed in Europe. In this study, we will evaluate the possible association between the MIC9D polymorphism and cognitive disorders. A genetic analysis of unrelated Sicilian patients with cognitive deficits was performed to identify the 9 bp deletion MIC9D polymorphism. The MIC9D polymorphism was found in six patients, whereas this variant was absent in control individuals without cognitive deficits. The patients with the MIC9D polymorphism exhibited more complex clinical presentations; in particular, all had neuromuscular disorders and five also presented with behavioral disorders. The present study suggests a potential association between the MIC9D polymorphism and cognitive impairment with concurrent neuromuscular and behavioral involvement.
PD-L1+ Lymphocytes Are Associated with CD4+, Foxp3+CD4+, IL17+CD4+ T Cells and Subtypes of Macrophages in Resected Early-Stage Non-Small Cell Lung Cancer
Authors: Gurevičienė Giedrė , Matulionė Jurgita , Poškienė Lina , Miliauskas Skaidrius , Žemaitis Marius
Published: October 2024

The non-canonical PD-L1 pathway revealed that programmed-death ligand 1 (PD-L1) expression in immune cells also plays a crucial role in immune response. Moreover, immune cell distribution in a tumour microenvironment (TME) is pivotal for tumour genesis. However, the results remain controversial and further research is needed. Distribution of PD-L1-positive (PD-L1+) tumour-infiltrating lymphocytes in the context of TME was assessed in 72 archival I–III stage surgically resected NSCLC tumour specimens. Predominant PD-L1+ lymphocyte distribution in the tumour stroma, compared to islets, was found (p = 0.01). Higher PD-L1+ lymphocyte infiltration was detected in smokers due to their predominance in the stroma. High PD-L1+ lymphocyte infiltration in tumour stroma was more common in tumours with higher CD4+ T cell infiltration in islets and stroma, Foxp3+CD4+ T cell infiltration in islets and lover M1 macrophage infiltration in the stroma (p = 0.034, p = 0.034, p = 0.005 and p = 0.034 respectively). Meanwhile, high PD-L1+ lymphocyte infiltration in islets was predominantly found in tumours with high levels of IL-17A+CD4+ T cells in islets and Foxp3+CD4+ T cells in islets and stroma (p = 0.032, p = 0.009 and p = 0.034, respectively). Significant correlations between PD-L1+ lymphocytes and tumour-infiltrating CD4+, Foxp3+CD4+, IL-17A+CD4+ T cells and M2 macrophages were found. An analysis of the tumour-immune phenotype revealed a significant association between PD-L1 expression and IL17+CD4+ and Foxp3+CD4+ immune phenotypes. PD-L1+ lymphocytes are associated with the distribution of CD4+, Foxp3+CD4+, IL17A+CD4+ T cells, M1 and M2 macrophages in TME of resected NSCLC.
Cyclodextrin-Containing Drug Delivery Systems and Their Applications in Neurodegenerative Disorders
Authors: Xing Yuan , Meng Bohan , Chen Qi
Published: October 2024

Cyclodextrins (CDs) are ubiquitous excipients, constituted of cyclic glucopyranose units, and possess a unique dual nature, that of a hydrophobic interior and a hydrophilic exterior. This enables their interaction with lipid-affinitive compounds and hydrophilic compounds, thereby augmenting their application in pharmaceutical formulations as agents for improving solubility, as well as fundamental elements of advanced drug delivery systems. Additionally, CDs, upon suitable modification, can strategically participate in the interaction with cellular components and physical barriers, such as the blood–brain barrier, where their intricate and multifunctional engagement leads to various biological impacts. This review consolidates the crucial features of CDs and their derivatives, and summarizes the applications of them as drug delivery systems in neurodegenerative disorders, emphasizing their notable potentials.
The Association of IFNL4 Gene Polymorphisms with Hepatitis B Virus (HBV) Infection in the Northern Region of Pará, Brazil
Authors: Andrade Álesson Adam Fonseca , Angelim Carolina Cabral , Martins Letícia Dias , Sacramento Amanda Roberta Vieira , Sousa Renata Santos de , Correa Raissa Lima , Conde Simone Regina Souza da Silva , Vallinoto Antonio Carlos Rosário , Feitosa Rosimar Neris Martins , Costa Greice de Lemos Cardoso
Published: October 2024

It is heavily suggested that one IFNL4 gene polymorphism, rs12979860 (T/C), exerts influence on the outcome of HBV infection, with the rs12979860-T allele being classified as a risk predictor, and the rs12979860-C allele being classified as a protective one. This study investigated whether the rs12979860 IFNL4 gene polymorphism presented any association with the clinical severity for HBV carriers in an admixed population in Northern Brazil. A total of 69 samples were investigated from infected people from the city of Belém-Pará. The rs12979860-T allele was positively associated with HBV infection, suggesting a higher risk of chronicity. This research’s importance is that the polymorphism influence was investigated in a population of HBV carriers with a heterogeneous genetic profile, formed through the extensive admixture of different ethnic groups, including Europeans, Africans, and Natives with indigenous heritage. This analysis is particularly important since highly mixed populations do not always follow the same association patterns previously established by studies using populations classified as more genetically homogeneous, due to a different formation process.
Genome-Wide Identification and Role of the bHLH Gene Family in Dendrocalamus latiflorus Flowering Regulation
Authors: Zeng Mei-Yin , Zhu Peng-Kai , Tang Yu , Lin Yu-Han , He Tian-You , Rong Jun-Dong , Zheng Yu-Shan , Chen Ling-Yan
Published: October 2024

The basic helix–loop–helix (bHLH) gene family is a crucial regulator in plants, orchestrating various developmental processes, particularly flower formation, and mediating responses to hormonal signals. The molecular mechanism of bamboo flowering regulation remains unresolved, limiting bamboo breeding efforts. In this study, we identified 309 bHLH genes and divided them into 23 subfamilies. Structural analysis revealed that proteins in specific DlbHLH subfamilies are highly conserved. Collinearity analysis indicates that the amplification of the DlbHLH gene family primarily occurs through segmental duplications. The structural diversity of these duplicated genes may account for their functional variability. Many DlbHLHs are expressed during flower development, indicating the bHLH gene’s significant role in this process. In the promoter region of DlbHLHs, different homeopathic elements involved in light response and hormone response co-exist, indicating that DlbHLHs are related to the regulation of the flower development of D. latiflorus.
3,8-Disubstituted Pyrazolo[1,5-a]quinazoline as GABAA Receptor Modulators: Synthesis, Electrophysiological Assays, and Molecular Modelling Studies
Authors: Crocetti Letizia , Guerrini Gabriella , Melani Fabrizio , Mascia Maria Paola , Giovannoni Maria Paola
Published: October 2024

As a continuation of our study in the field of GABAA receptor modulators, we report the design and synthesis of new pyrazolo[1,5-a]quinazoline (PQ) bearing at the 8-position an oxygen or nitrogen function. All the final compounds and some intermediates, showing the three different forms of the pyrazolo[1,5-a]quinazoline scaffold (5-oxo-4,5-dihydro, -4,5-dihydro, and heteroaromatic form), have been screened with an electrophysiological technique on recombinant GABAAR (α1β2γ2-GABAAR), expressed in Xenopus laevis oocytes, by evaluating the variation in produced chlorine current, and permitting us to identify some interesting compounds (6d, 8a, 8b, and 14) on which further functional assays were performed. Molecular modelling studies (docking, minimization of complex ligand–receptor, and MD model) and a statistical analysis by a Hierarchical Cluster Analysis (HCA) have collocated these ligands in the class corresponding to their pharmacological profile. The HCA results are coherent with the model we recently published (Proximity Frequencies), identifying the residues γThr142 and αHis102 as discriminant for the agonist and antagonist profile.
Challenging Diagnosis of a Patient with Two Novel Variants in the SYNE1 Gene
Authors: Kuchina Anna , Murtazina Aysylu , Borovikov Artem , Subbotin Dmitrii , Bardakov Sergey , Akhkiamova Maria , Nikolaeva Aleksandra , Shchagina Olga , Kutsev Sergey
Published: October 2024

We report a case of SYNE1-associated autosomal recessive spinocerebellar ataxia (SCAR8) presenting with a complex multisystemic phenotype, including highly elevated creatine kinase levels and lower-leg muscle atrophy. In addition to identifying two novel pathogenic variants in the SYNE1 gene, whole-exome sequencing revealed three variants of uncertain significance in the DYSF gene. Electromyography and muscle magnetic resonance imaging indicated a neurogenic pattern of muscle involvement. These findings, along with the segregation analysis of the variants, allowed us to exclude DYSF-associated muscular dystrophy; however, we cannot entirely rule out the possibility that the DYSF gene variants may act as modifiers of the patient’s phenotype.
A Rare Case of TP63-Associated Lymphopenia Revealed by Newborn Screening Using TREC
Authors: Marakhonov Andrey , Serebryakova Elena , Mukhina Anna , Vechkasova Anastasia , Prokhorov Nikolai , Efimova Irina , Balinova Natalia , Lobenskaya Anastasia , Vasilyeva Tatyana , Zabnenkova Victoria , Ryzhkova Oxana , Rodina Yulia , Pershin Dmitry , Soloveva Nadezhda , Fomenko Anna , Saydaeva Djamila , Ibisheva Aset , Irbaieva Taisiya , Koroteev Alexander , Zinchenko Rena , Voronin Sergey , Shcherbina Anna , Kutsev Sergey
Published: October 2024

The expanded newborn screening (NBS) program in the Russian Federation was initiated in 2023, among which severe combined immunodeficiency (SCID) is screened using TREC/KREC assays. Here, we report a rare case of a TP63-associated disease identified through this NBS program. Dried blood spots from newborns were initially screened for TREC/KREC levels, and those with values below the cut-off underwent confirmatory testing and further genetic analysis, including whole-exome sequencing (WES). A male newborn was identified with significantly reduced TREC values, indicative of T cell lymphopenia. Genetic analysis revealed a heterozygous NM_003722.5:c.1027C>T variant in TP63, leading to the p.(Arg343Trp) substitution within the DNA binding domain. This mutation has been previously associated with Ectrodactyly–Ectodermal Dysplasia–Cleft lip/palate syndrome (EEC) syndrome and shown to reduce the transactivation activity of TP63 in a dominant-negative manner. This case represents one of the few instances of immune system involvement in a patient with a TP63 mutation, highlighting the need for further investigation into the immunological aspects of TP63-associated disorders. Our findings suggest that comprehensive immunological evaluation should be considered for patients with TP63 mutations to better understand and manage potential immune dysfunctions.
DNA Methylation Negatively Regulates Gene Expression of Key Cytokines Secreted by BMMCs Recognizing FMDV-VLPs
Authors: Li Mingzhu , Ning Peng , Bai Ruoman , Tian Zhanyun , Liu Shujia , Li Limin
Published: October 2024

Virus-like particles (VLPs) have been studied and used as vaccines to control foot-and-mouth disease (FMD). Mast cells (MCs) express various pattern recognition receptors that recognize pathogens and secrete numerous cytokines to initiate and modulate immune responses. Our previous study showed that bone marrow-derived mast cells (BMMCs) can recognize foot-and-mouth disease virus-like particles (FMDV-VLPs) to differentially express various cytokines and that histone acetylation can regulate the cytokines secreted during BMMC recognition of FMDV-VLPs. To demonstrate the role of DNA methylation in this response process, BMMCs that recognize FMDV-VLPs were treated with azacytidine (5-AZA), an inhibitor of DNA methylation transferase. We prepared FMDV-VLPs as described previously and cultured the BMMCs. The transcription and expression of key cytokines and transcription factors were determined using real-time quantitative PCR (RT-qPCR) and Western blotting. Results showed that pre-treatment with AZA resulted in the increased transcription and expression of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-13, and IL-10, while the changes in IL-13 transcription and IL-6 expression were irrelevant to mannose receptors (MRs). Furthermore, analysis of the transcription factors indicated that both the transcription and expression of nuclear factor-kappa B (NF-κB) increased significantly in the AZA pre-treated group, indicating that DNA methylation may also regulate NF-κB expression to modulate TNF-α, IL-13, and IL-6. However, pre-treatment with AZA did not alter the expression of microphthalmia-associated transcription factor (MITF) or GATA-2. All the data demonstrate that DNA methylation negatively regulates the transcription and expression of TNF-α, IL-13, IL-10, and IL-6 secreted by recognizing FMDV-VLPs. These results provide new ideas for the mast cell-based design of more effective vaccine adjuvants and targeted therapies in the future.
Protective Potential of Cicerbita alpina Leaf Extract on Metabolic Disorders and Oxidative Stress in Model Animals
Authors: Zheleva-Dimitrova Dimitrina , Petrova Alexandra , Savov Yonko , Gevrenova Reneta , Balabanova Vessela , Momekov Georgi , Simeonova Rumyana
Published: October 2024

Metabolic disorders (MDs) include disease states such as diabetes mellitus, obesity, dyslipidemia, hyperuricemia, etc., affecting about 30% of the planet’s population. The purpose of the present study was to investigate the protective potential of Cicerbita alpina leaf extract (ECA) against chemically induced type 2 diabetes in Wistar rats. Additionally, some biochemical parameters in the blood serum and liver, as well as histopathological investigation, were also performed. Quantitative analysis of the major compounds in the used extract was performed using ultrahigh-performance liquid chromatography-diode array detection (UHPLC-DAD) analyses using the external standard method. C. alpina extract revealed a beneficial effect on MDs, lowering blood sugar levels and MDA quantity in the liver, increasing the reduced glutathione level, and increasing antioxidant enzyme activity. Cichoric acid (CA) (91.93 mg/g dry extract (de) ± 4.64 mg/g de) was found to be the dominant compound in the extract, followed by caftaric (11.36 ± 2.10 mg/g de), and chlorogenic acid (CGA) (9.25 ± 0.05 mg/g de). In conclusion, C. alpina leaf extract (ECA) is rich in caffeoyltartaric and caffeoylquinic acids and provides beneficial effects on the diabetic animal model.
Genome-Scale Metabolic Models in Fungal Pathogens: Past, Present, and Future
Authors: Fonseca-Fernández Angie Lorena , González Barrios Andrés Fernando , Celis Ramírez Adriana Marcela
Published: October 2024

Fungi are diverse organisms with various characteristics and functions. Some play a role in recycling essential elements, such as nitrogen and carbon, while others are utilized in the food and drink production industry. Some others are known to cause diseases in various organisms, including humans. Fungal pathogens cause superficial, subcutaneous, and systemic infections. Consequently, many scientists have focused on studying the factors contributing to the development of human diseases. Therefore, multiple approaches have been assessed to examine the biology of these intriguing organisms. The genome-scale metabolic models (GEMs) have demonstrated many advantages to microbial metabolism studies and the ability to propose novel therapeutic alternatives. Despite significant advancements, much remains to be elucidated regarding the use of this tool for investigating fungal metabolism. This review aims to compile the data provided by the published GEMs of human fungal pathogens. It gives specific examples of the most significant contributions made by these models, examines the advantages and difficulties associated with using such models, and explores the novel approaches suggested to enhance and refine their development.
Advances in Gouty Arthritis Management: Integration of Established Therapies, Emerging Treatments, and Lifestyle Interventions
Authors: Yao Ting-Kuo , Lee Ru-Ping , Wu Wen-Tien , Chen Ing-Ho , Yu Tzai-Chiu , Yeh Kuang-Ting
Published: October 2024

Gouty arthritis, a prevalent inflammatory condition characterized by the deposition of monosodium urate crystals within joints, often results in debilitating pain and inflammation. Conventional therapeutic approaches, including nonsteroidal anti-inflammatory drugs, corticosteroids, and urate-lowering agents such as allopurinol and febuxostat, often have limitations such as adverse effects, drug interactions, and suboptimal patient compliance. This review presents a comprehensive overview of both established and emerging therapeutic strategies, developed between 2019 and 2024, for gouty arthritis; the review focuses on their mechanisms of action, efficacy, and safety profiles. Novel therapeutic approaches include pharmaceutical plant additives (e.g., Citrullus colocynthis, Atractylodes lancea), anti-inflammatory agents such as canakinumab and ozone therapy, and complementary therapies such as warm ginger compresses, Qingpeng ointment, and various lifestyle modifications. These strategies offer promising alternatives to conventional treatments by targeting uric acid metabolism, inflammatory pathways, and crystal formation, potentially reducing reliance on standard medications and minimizing adverse effects. Although therapies such as canakinumab have demonstrated significant efficacy in reducing gout flares, others such as polyphenol-rich foods offer favorable safety profiles. Further research, including large-scale clinical trials, is warranted to validate these findings and integrate these strategies into clinical practice to improve patient outcomes and quality of life.
Chemokine Receptor N-Terminus Charge Dictates Reliance on Post-Translational Modifications for Effective Ligand Capture and Following Boosting by Defense Peptides
Authors: Xu Ting , Schou Anne Sophie , Lackman Jarkko J. , Barrio-Calvo Marina , Verhallen Lisa , Goth Christoffer Knak , Jensen Benjamin Anderschou Holbech , Veldkamp Christopher T. , Volkman Brian F. , Peterson Francis C. , Hjortø Gertrud Malene
Published: October 2024

The chemokine receptors CCR1 and CCR5 display overlapping expression patterns and ligand dependency. Here we find that ligand activation of CCR5, not CCR1, is dependent on N-terminal receptor O-glycosylation. Release from O-glycosylation dependency is obtained by increasing CCR5 N-terminus acidity to the level of CCR1. Ligand activation of CCR5, not CCR1, drastically improves in the absence of glycosaminoglycans (GAGs). Ligand activity at both CCR1 and CCR5 is boosted by positively charged/basic peptides shown to interact with acidic chemokine receptor N-termini. We propose that receptors with an inherent low N-terminus acidity rely on post-translational modifications (PTMs) to efficiently compete with acidic entities in the local environment for ligand capture. Although crucial for initial ligand binding, strong electrostatic interactions between the ligand and the receptor N-terminus may counteract following insertion of the ligand into the receptor binding pocket and activation, a process that seems to be aided in the presence of basic peptides. Basic peptides bind to the naked CCR1 N-terminus, not the CCR5 N-terminus, explaining the loss of boosting of ligand-induced signaling via CCR5 in cells incapable of glycosylation.
The Expression of miR-211-5p in Sentinel Lymph Node Metastases of Malignant Melanoma Is a Potential Marker for Poor Prognosis
Authors: Moritz Rose Kathrin Caroline , Ebelt Nicole , Rattay Tina , Ehrenreich Jovine , Sunderkötter Cord , Gerloff Dennis
Published: October 2024

Metastatic primary cutaneous melanoma is a frequently fatal disease despite recent therapeutic advances. Biomarkers to stratify patients’ prognosis are lacking. MicroRNAs (miRNAs) are small, non-coding RNAs. We aimed to determine the expression of miR-211-5p in primary tumors and metastases of malignant melanoma and its potential use as a prognostic biomarker. We performed in situ hybridization for miRNA-211-5p on 109 FFPE melanoma samples from 76 patients, including 31 paired primary tumor/metastasis samples. For validation, we performed in silico analyses of TCGA skin cutaneous melanoma (SKCM) cohort. High miR-211-5p expression was more frequent in primary tumors (70.8%) compared to metastases (39.3%). In metastases, it was associated with a significantly worse overall survival. Data from TCGA SKCM cohort confirmed that high miR-211-5p expression in melanoma metastases, but not primary tumors, is associated with worse overall survival. MiR-211-5p expression in metastases is associated with a shorter survival, emphasizing the potential of miR-211-5p as a risk predictor for a less favorable clinical outcome in metastatic disease. In situ hybridization could be implemented in a routine laboratory workflow and can be performed on diagnostic tissue.
Analysis of ICAM-1 rs3093030, VCAM-1 rs3783605, and E-Selectin rs1805193 Polymorphisms in African Women Living with HIV and Preeclampsia
Authors: Sibiya Samukelisiwe , Mlambo Zinhle Pretty , Mthembu Mbuso Herald , Mkhwanazi Nompumelelo P. , Naicker Thajasvarie
Published: October 2024

Intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin are cell adhesion molecules that play a significant role in inflammation and are implicated in the pathophysiology of preeclampsia development and HIV infection. More specifically, the immune expression of ICAM-1, VCAM-1, and E-selectin within cyto- and syncytiotrophoblast cells are dysregulated in preeclampsia, indicating their role in defective placentation. This study investigates the associations of ICAM-1, VCAM-1, and E-selectin gene variants (rs3093030, rs3783605, and rs1805193, respectively) with preeclampsia comorbid with HIV infection in women of African ancestry. It also examines the susceptibility to preeclampsia development and the effect of highly active antiretroviral therapy (HAART). A total of 405 women were enrolled in this study. Out of these women, 204 were preeclamptic and 201 were normotensive. Clinical characteristics were maternal age, weight, blood pressure (systolic and diastolic), and gestational age. Whole blood was collected, DNA was extracted, and genotyping of the ICAM-1 (rs3093030 C>T), VCAM-1(rs3783605 A>G), and E-selectin (rs1805193 A>C) gene polymorphisms was performed. Comparisons were made using the Chi-squared test. Our results demonstrated that preeclamptic women exhibited a higher frequency of analyzed variants, in contrast to those with the duality of preeclampsia and HIV infection. Additionally, the C allele of the ICAM-1 (rs3093030 C>T) and G allele of the VCAM-1 (rs3783605 A>G) genes were found to have a greater role in the co-morbidity and may be considered as a risk factor for preeclampsia development in women of African ancestry. In contrast, the SNP of rs1805193 of the E-selectin gene indicated that A>C was only significantly associated with HIV infection and not with preeclampsia. These findings highlight a strong association of the rs3093030 SNP of the ICAM-1 gene and of the VCAM-1 rs3783605 gene with the development of preeclampsia, indicating their role in the defective trophoblast invasion of preeclampsia. Sub-group analysis further reveals an association of the AA genotype with late-onset preeclampsia, a less severe form of disease indicating differing genetic predispositions between early and late-onset forms.