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21 pages, 4314 KiB  
Article
Panoptic Plant Recognition in 3D Point Clouds: A Dual-Representation Learning Approach with the PP3D Dataset
by Lin Zhao, Sheng Wu, Jiahao Fu, Shilin Fang, Shan Liu and Tengping Jiang
Remote Sens. 2025, 17(15), 2673; https://doi.org/10.3390/rs17152673 (registering DOI) - 2 Aug 2025
Abstract
The advancement of Artificial Intelligence (AI) has significantly accelerated progress across various research domains, with growing interest in plant science due to its substantial economic potential. However, the integration of AI with digital vegetation analysis remains underexplored, largely due to the absence of [...] Read more.
The advancement of Artificial Intelligence (AI) has significantly accelerated progress across various research domains, with growing interest in plant science due to its substantial economic potential. However, the integration of AI with digital vegetation analysis remains underexplored, largely due to the absence of large-scale, real-world plant datasets, which are crucial for advancing this field. To address this gap, we introduce the PP3D dataset—a meticulously labeled collection of about 500 potted plants represented as 3D point clouds, featuring fine-grained annotations for approximately 20 species. The PP3D dataset provides 3D phenotypic data for about 20 plant species spanning model organisms (e.g., Arabidopsis thaliana), potted plants (e.g., Foliage plants, Flowering plants), and horticultural plants (e.g., Solanum lycopersicum), covering most of the common important plant species. Leveraging this dataset, we propose the panoptic plant recognition task, which combines semantic segmentation (stems and leaves) with leaf instance segmentation. To tackle this challenge, we present SCNet, a novel dual-representation learning network designed specifically for plant point cloud segmentation. SCNet integrates two key branches: a cylindrical feature extraction branch for robust spatial encoding and a sequential slice feature extraction branch for detailed structural analysis. By efficiently propagating features between these representations, SCNet achieves superior flexibility and computational efficiency, establishing a new baseline for panoptic plant recognition and paving the way for future AI-driven research in plant science. Full article
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24 pages, 6639 KiB  
Article
CNS Axon Regeneration in the Long Primary Afferent System in E15/E16 Hypoxic-Conditioned Fetal Rats: A Thrust-Driven Concept
by Frits C. de Beer and Harry W. M. Steinbusch
Anatomia 2025, 4(3), 12; https://doi.org/10.3390/anatomia4030012 - 1 Aug 2025
Viewed by 48
Abstract
Background: Lower phylogenetic species are known to rebuild cut-off caudal parts with regeneration of the central nervous system (CNS). In contrast, CNS regeneration in higher vertebrates is often attributed to immaturity, although this has never been conclusively demonstrated. The emergence of stem cells [...] Read more.
Background: Lower phylogenetic species are known to rebuild cut-off caudal parts with regeneration of the central nervous system (CNS). In contrast, CNS regeneration in higher vertebrates is often attributed to immaturity, although this has never been conclusively demonstrated. The emergence of stem cells and their effective medical applications has intensified research into spinal cord regeneration. However, despite these advances, the impact of clinical trials involving spinal cord-injured (SCI) patients remains disappointingly low. Long-distance regeneration has yet to be proven. Methods: Our study involved a microsurgical dorsal myelotomy in fetal rats. The development of pioneering long primary afferent axons during early gestation was examined long after birth. Results: A single cut triggered the intrinsic ability of the dorsal root ganglion (DRG) neurons to reprogram. Susceptibility to hypoxia caused the axons to stop developing. However, the residual axonal outgrowth sheds light on the intriguing temporal and spatial events that reveal long-distance CNS regeneration. The altered phenotypes displayed axons of varying lengths and different features, which remained visible throughout life. The previously designed developmental blueprint was crucial for interpreting these enigmatic features. Conclusions: This research into immaturity enabled the exploration of the previously impenetrable domain of early life and the identification of a potential missing link in CNS regeneration research. Central axon regeneration appeared to occur much faster than is generally believed. The paradigm provides a challenging approach for exhaustive intrauterine reprogramming. When the results demonstrate pre-clinical effectiveness in CNS regeneration research, the transformational impact may ultimately lead to improved outcomes for patients with spinal cord injuries. Full article
(This article belongs to the Special Issue From Anatomy to Clinical Neurosciences)
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17 pages, 902 KiB  
Review
Cancer Stem Cells in Melanoma: Drivers of Tumor Plasticity and Emerging Therapeutic Strategies
by Adrian-Horațiu Sabău, Andreea-Cătălina Tinca, Raluca Niculescu, Iuliu Gabriel Cocuz, Andreea Raluca Cozac-Szöke, Bianca Andreea Lazar, Diana Maria Chiorean, Corina Eugenia Budin and Ovidiu Simion Cotoi
Int. J. Mol. Sci. 2025, 26(15), 7419; https://doi.org/10.3390/ijms26157419 (registering DOI) - 1 Aug 2025
Viewed by 80
Abstract
Cutaneous malignant melanoma is an extraordinarily aggressive and heterogeneous cancer that contains a small subpopulation of tumor stem cells (CSCs) responsible for tumor initiation, metastasis, and recurrence. Identification and characterization of CSCs in melanoma is challenging due to tumor heterogeneity and the lack [...] Read more.
Cutaneous malignant melanoma is an extraordinarily aggressive and heterogeneous cancer that contains a small subpopulation of tumor stem cells (CSCs) responsible for tumor initiation, metastasis, and recurrence. Identification and characterization of CSCs in melanoma is challenging due to tumor heterogeneity and the lack of specific markers (CD271, ABCB5, ALDH, Nanog) and the ability of cells to dynamically change their phenotype. Phenotype-maintaining signaling pathways (Wnt/β-catenin, Notch, Hedgehog, HIF-1) promote self-renewal, treatment resistance, and epithelial–mesenchymal transitions. Tumor plasticity reflects the ability of differentiated cells to acquire stem-like traits and phenotypic flexibility under stress conditions. The interaction of CSCs with the tumor microenvironment accelerates disease progression: they induce the formation of cancer-associated fibroblasts (CAFs) and neo-angiogenesis, extracellular matrix remodeling, and recruitment of immunosuppressive cells, facilitating immune evasion. Emerging therapeutic strategies include immunotherapy (immune checkpoint inhibitors), epigenetic inhibitors, and nanotechnologies (targeted nanoparticles) for delivery of chemotherapeutic agents. Understanding the role of CSCs and tumor plasticity paves the way for more effective innovative therapies against melanoma. Full article
(This article belongs to the Special Issue Mechanisms of Resistance to Melanoma Immunotherapy)
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14 pages, 1813 KiB  
Article
Elevated Antigen-Presenting-Cell Signature Genes Predict Stemness and Metabolic Reprogramming States in Glioblastoma
by Ji-Yong Sung and Kihwan Hwang
Int. J. Mol. Sci. 2025, 26(15), 7411; https://doi.org/10.3390/ijms26157411 (registering DOI) - 1 Aug 2025
Viewed by 148
Abstract
Glioblastoma (GBM) is a highly aggressive and heterogeneous brain tumor. Glioma stem-like cells (GSCs) play a central role in tumor progression, therapeutic resistance, and recurrence. Although immune cells are known to shape the GBM microenvironment, the impact of antigen-presenting-cell (APC) signature genes on [...] Read more.
Glioblastoma (GBM) is a highly aggressive and heterogeneous brain tumor. Glioma stem-like cells (GSCs) play a central role in tumor progression, therapeutic resistance, and recurrence. Although immune cells are known to shape the GBM microenvironment, the impact of antigen-presenting-cell (APC) signature genes on tumor-intrinsic phenotypes remains underexplored. We analyzed both bulk- and single-cell RNA sequencing datasets of GBM to investigate the association between APC gene expression and tumor-cell states, including stemness and metabolic reprogramming. Signature scores were computed using curated gene sets related to APC activity, KEGG metabolic pathways, and cancer hallmark pathways. Protein–protein interaction (PPI) networks were constructed to examine the links between immune regulators and metabolic programs. The high expression of APC-related genes, such as HLA-DRA, CD74, CD80, CD86, and CIITA, was associated with lower stemness signatures and enhanced inflammatory signaling. These APC-high states (mean difference = –0.43, adjusted p < 0.001) also showed a shift in metabolic activity, with decreased oxidative phosphorylation and increased lipid and steroid metabolism. This pattern suggests coordinated changes in immune activity and metabolic status. Furthermore, TNF-α and other inflammatory markers were more highly expressed in the less stem-like tumor cells, indicating a possible role of inflammation in promoting differentiation. Our findings revealed that elevated APC gene signatures are associated with more differentiated and metabolically specialized GBM cell states. These transcriptional features may also reflect greater immunogenicity and inflammation sensitivity. The APC metabolic signature may serve as a useful biomarker to identify GBM subpopulations with reduced stemness and increased immune engagement, offering potential therapeutic implications. Full article
(This article belongs to the Special Issue Advanced Research on Cancer Stem Cells)
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20 pages, 5322 KiB  
Article
Regulation of Tetraspanin CD63 in Chronic Myeloid Leukemia (CML): Single-Cell Analysis of Asymmetric Hematopoietic Stem Cell Division Genes
by Christophe Desterke, Annelise Bennaceur-Griscelli and Ali G. Turhan
Bioengineering 2025, 12(8), 830; https://doi.org/10.3390/bioengineering12080830 (registering DOI) - 31 Jul 2025
Viewed by 170
Abstract
(1) Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the BCR::ABL oncoprotein. During the chronic phase, Philadelphia chromosome-positive hematopoietic stem cells generate proliferative myeloid cells with various stages of maturation. Despite this expansion, leukemic stem cells (LSCs) retain self-renewal capacity [...] Read more.
(1) Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder driven by the BCR::ABL oncoprotein. During the chronic phase, Philadelphia chromosome-positive hematopoietic stem cells generate proliferative myeloid cells with various stages of maturation. Despite this expansion, leukemic stem cells (LSCs) retain self-renewal capacity via asymmetric cell divisions, sustaining the stem cell pool. Quiescent LSCs are known to be resistant to tyrosine kinase inhibitors (TKIs), potentially through BCR::ABL-independent signaling pathways. We hypothesize that dysregulation of genes governing asymmetric division in LSCs contributes to disease progression, and that their expression pattern may serve as a prognostic marker during the chronic phase of CML. (2) Methods: Genes related to asymmetric cell division in the context of hematopoietic stem cells were extracted from the PubMed database with the keyword “asymmetric hematopoietic stem cell”. The collected relative gene set was tested on two independent bulk transcriptome cohorts and the results were confirmed by single-cell RNA sequencing. (3) Results: The expression of genes involved in asymmetric hematopoietic stem cell division was found to discriminate disease phases during CML progression in the two independent transcriptome cohorts. Concordance between cohorts was observed on asymmetric molecules downregulated during blast crisis (BC) as compared to the chronic phase (CP). This downregulation during the BC phase was confirmed at single-cell level for SELL, CD63, NUMB, HK2, and LAMP2 genes. Single-cell analysis during the CP found that CD63 is associated with a poor prognosis phenotype, with the opposite prediction revealed by HK2 and NUMB expression. The single-cell trajectory reconstitution analysis in CP samples showed CD63 regulation highlighting a trajectory cluster implicating HSPB1, PIM2, ANXA5, LAMTOR1, CFL1, CD52, RAD52, MEIS1, and PDIA3, known to be implicated in hematopoietic malignancies. (4) Conclusion: Regulation of CD63, a tetraspanin involved in the asymmetric division of hematopoietic stem cells, was found to be associated with poor prognosis during CML progression and could be a potential new therapeutic target. Full article
(This article belongs to the Special Issue Micro- and Nano-Technologies for Cell Analysis)
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16 pages, 5301 KiB  
Article
TSINet: A Semantic and Instance Segmentation Network for 3D Tomato Plant Point Clouds
by Shanshan Ma, Xu Lu and Liang Zhang
Appl. Sci. 2025, 15(15), 8406; https://doi.org/10.3390/app15158406 - 29 Jul 2025
Viewed by 126
Abstract
Accurate organ-level segmentation is essential for achieving high-throughput, non-destructive, and automated plant phenotyping. To address the challenge of intelligent acquisition of phenotypic parameters in tomato plants, we propose TSINet, an end-to-end dual-task segmentation network designed for effective and precise semantic labeling and instance [...] Read more.
Accurate organ-level segmentation is essential for achieving high-throughput, non-destructive, and automated plant phenotyping. To address the challenge of intelligent acquisition of phenotypic parameters in tomato plants, we propose TSINet, an end-to-end dual-task segmentation network designed for effective and precise semantic labeling and instance recognition of tomato point clouds, based on the Pheno4D dataset. TSINet adopts an encoder–decoder architecture, where a shared encoder incorporates four Geometry-Aware Adaptive Feature Extraction Blocks (GAFEBs) to effectively capture local structures and geometric relationships in raw point clouds. Two parallel decoder branches are employed to independently decode shared high-level features for the respective segmentation tasks. Additionally, a Dual Attention-Based Feature Enhancement Module (DAFEM) is introduced to further enrich feature representations. The experimental results demonstrate that TSINet achieves superior performance in both semantic and instance segmentation, particularly excelling in challenging categories such as stems and large-scale instances. Specifically, TSINet achieves 97.00% mean precision, 96.17% recall, 96.57% F1-score, and 93.43% IoU in semantic segmentation and 81.54% mPrec, 81.69% mRec, 81.60% mCov, and 86.40% mWCov in instance segmentation. Compared with state-of-the-art methods, TSINet achieves balanced improvements across all metrics, significantly reducing false positives and false negatives while enhancing spatial completeness and segmentation accuracy. Furthermore, we conducted ablation studies and generalization tests to systematically validate the effectiveness of each TSINet component and the overall robustness of the model. This study provides an effective technological approach for high-throughput automated phenotyping of tomato plants, contributing to the advancement of intelligent agricultural management. Full article
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18 pages, 1278 KiB  
Review
Metabolic Maturation in hiPSC-Derived Cardiomyocytes: Emerging Strategies for Inducing the Adult Cardiac Phenotype
by Daniela Malan, Maria Pia Gallo, Federica Geddo, Renzo Levi and Giulia Querio
Pharmaceuticals 2025, 18(8), 1133; https://doi.org/10.3390/ph18081133 - 29 Jul 2025
Viewed by 230
Abstract
Human induced pluripotent stem cells (hiPSCs) are widely used in basic research because of their versatility and ability to differentiate into multiple cell types. In particular, differentiating hiPSCs into cardiac cells (hiPSC-CMs) has been an important milestone in cardiac pathophysiology studies. Although hiPSC-CMs [...] Read more.
Human induced pluripotent stem cells (hiPSCs) are widely used in basic research because of their versatility and ability to differentiate into multiple cell types. In particular, differentiating hiPSCs into cardiac cells (hiPSC-CMs) has been an important milestone in cardiac pathophysiology studies. Although hiPSC-CMs offer a model for human cardiomyocytes, they still exhibit characteristics linked to the fetal cardiac cell phenotype. One important feature that prevents hiPSC-CMs from being identified as adult cells relates to their metabolism, which is a key factor in defining a mature phenotype capable of sustaining the workload requirements characteristic of fully differentiated cardiomyocytes. This review aims to present the most relevant strategies in terms of culture medium composition, culture times, and 3D culture methods that have been developed to promote the metabolic maturation of hiPSC-CMs, which are now widely used. Defining a standardized and universally accepted protocol would enable the creation of a cellular model for studies of cardiac pathophysiology from a patient-specific perspective and for drug screening. Full article
(This article belongs to the Special Issue Cell Therapy for Cardiac Disease)
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24 pages, 6108 KiB  
Review
Angiogenic Cell Precursors and Neural Cell Precursors in Service to the Brain–Computer Interface
by Fraser C. Henderson and Kelly Tuchman
Cells 2025, 14(15), 1163; https://doi.org/10.3390/cells14151163 - 29 Jul 2025
Viewed by 372
Abstract
The application of artificial intelligence through the brain–computer interface (BCI) is proving to be one of the great advances in neuroscience today. The development of surface electrodes over the cortex and very fine electrodes that can be stereotactically implanted in the brain have [...] Read more.
The application of artificial intelligence through the brain–computer interface (BCI) is proving to be one of the great advances in neuroscience today. The development of surface electrodes over the cortex and very fine electrodes that can be stereotactically implanted in the brain have moved the science forward to the extent that paralyzed people can play chess and blind people can read letters. However, the introduction of foreign bodies into deeper parts of the central nervous system results in foreign body reaction, scarring, apoptosis, and decreased signaling. Implanted electrodes activate microglia, causing the release of inflammatory factors, the recruitment of systemic inflammatory cells to the site of injury, and ultimately glial scarring and the encapsulation of the electrode. Recordings historically fail between 6 months and 1 year; the longest BCI in use has been 7 years. This article proposes a biomolecular strategy provided by angiogenic cell precursors (ACPs) and nerve cell precursors (NCPs), administered intrathecally. This combination of cells is anticipated to sustain and promote learning across the BCI. Together, through the downstream activation of neurotrophic factors, they may exert a salutary immunomodulatory suppression of inflammation, anti-apoptosis, homeostasis, angiogenesis, differentiation, synaptogenesis, neuritogenesis, and learning-associated plasticity. Full article
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23 pages, 4112 KiB  
Article
Metabolic Culture Medium Enhances Maturation of Human iPSC-Derived Cardiomyocytes via Cardiac Troponin I Isoform Induction
by Daria V. Goliusova, Agnessa P. Bogomolova, Alina V. Davidenko, Kristina A. Lavrenteva, Margarita Y. Sharikova, Elena A. Zerkalenkova, Ekaterina M. Vassina, Alexandra N. Bogomazova, Maria A. Lagarkova, Ivan A. Katrukha and Olga S. Lebedeva
Int. J. Mol. Sci. 2025, 26(15), 7248; https://doi.org/10.3390/ijms26157248 - 26 Jul 2025
Viewed by 424
Abstract
Human induced pluripotent stem cell-derived cardiomyocytes (iCMs) provide a powerful platform for investigating cardiac biology. However, structural, metabolic, and electrophysiological immaturity of iCMs limits their capacity to model adult cardiomyocytes. Currently, no universally accepted criteria or protocols for effective iCMs maturation exist. This [...] Read more.
Human induced pluripotent stem cell-derived cardiomyocytes (iCMs) provide a powerful platform for investigating cardiac biology. However, structural, metabolic, and electrophysiological immaturity of iCMs limits their capacity to model adult cardiomyocytes. Currently, no universally accepted criteria or protocols for effective iCMs maturation exist. This study aimed to identify practical culture conditions that promote iCMs maturation, thereby generating more physiologically relevant in vitro cardiac models. We evaluated the effects of short- and long-term culture in media supplemented with various stimulatory compounds under 2D conditions, focusing on intracellular content and localization of slow skeletal troponin I (ssTnI) and cardiac troponin I (cTnI) isoforms. Our findings demonstrate that the multicomponent metabolic maturation medium (MM-1) effectively enhances the transition toward a more mature iCM phenotype, as evidenced by increased cTnI expression and formation of cross-striated myofibrils. iCMs cultured in MM-1 more closely resemble adult cardiomyocytes and are compatible with high-resolution single-cell techniques such as electron microscopy and patch-clamp electrophysiology. This work provides a practical and scalable approach for advancing the maturation of iPSC-derived cardiac models, with applications in disease modeling and drug screening. Full article
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20 pages, 17373 KiB  
Article
The Memory Gene, Murashka, Is a Regulator of Notch Signalling and Controls the Size of the Drosophila Germline Stem Cell Niche
by Thifeen Deen, Hideyuki Shimizu, Marian B. Wilkin and Martin Baron
Biomolecules 2025, 15(8), 1082; https://doi.org/10.3390/biom15081082 - 26 Jul 2025
Viewed by 339
Abstract
We identified Murashka, a RING finger protein, in an oogenesis screen as a regulator of Drosophila ovary germline stem cell niche development. Mutant alleles of murashka exhibited an enlarged niche phenotype reminiscent of increased Notch signalling and displayed genetic interactions with Notch alleles, [...] Read more.
We identified Murashka, a RING finger protein, in an oogenesis screen as a regulator of Drosophila ovary germline stem cell niche development. Mutant alleles of murashka exhibited an enlarged niche phenotype reminiscent of increased Notch signalling and displayed genetic interactions with Notch alleles, and with polychaetoid, a regulator of Notch during niche development. These interactions uncovered both positive and negative impacts on Notch in different genetic backgrounds. In S2 cells, Murashka formed a complex with Notch and colocalised with Notch in the secretory pathway. Murashka expression in S2 cells down-regulated Notch signalling levels but could result in increased fold induction due to the proportionally greater decrease in basal ligand-independent activity. In vivo Murashka expression had different outcomes on different Notch target genes. We observed a decrease in the expression of vestigial along the anterior/posterior boundary of the wing imaginal disc, but not of wingless at the dorsal/ventral boundary. Instead, weak ectopic wingless was observed, which was synergistically increased by the coexpression of Deltex, a positive regulator of ligand-independent signalling. Our results identify a novel developmental role for murashka, a gene previously only associated with a function in long-term memory, and indicate a regulatory role for Murashka through a physical interaction with Notch that has context-dependent outcomes. Murashka adds to a growing number of ubiquitin ligase regulators which interact with Notch at different locations within its secretory and endocytic trafficking pathways. Full article
(This article belongs to the Special Issue Notch and Its Regulation in Health and Disease)
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18 pages, 12946 KiB  
Article
High-Resolution 3D Reconstruction of Individual Rice Tillers for Genetic Studies
by Jiexiong Xu, Jiyoung Lee, Gang Jiang and Xiangchao Gan
Agronomy 2025, 15(8), 1803; https://doi.org/10.3390/agronomy15081803 - 25 Jul 2025
Viewed by 186
Abstract
The architecture of rice tillers plays a pivotal role in yield potential, yet conventional phenotyping methods have struggled to capture these intricate three-dimensional (3D) structures with high fidelity. In this study, a 3D model reconstruction method was developed specifically for rice tillers to [...] Read more.
The architecture of rice tillers plays a pivotal role in yield potential, yet conventional phenotyping methods have struggled to capture these intricate three-dimensional (3D) structures with high fidelity. In this study, a 3D model reconstruction method was developed specifically for rice tillers to overcome the challenges posed by their slender, feature-poor morphology in multi-view stereo-based 3D reconstruction. By applying strategically designed colorful reference markers, high-resolution 3D tiller models of 231 rice landraces were reconstructed. Accurate phenotyping was achieved by introducing ScaleCalculator, a software tool that integrated depth images from a depth camera to calibrate the physical sizes of the 3D models. The high efficiency of the 3D model-based phenotyping pipeline was demonstrated by extracting the following seven key agronomic traits: flag leaf length, panicle length, first internode length below the panicle, stem length, flag leaf angle, second leaf angle from the panicle, and third leaf angle. Genome-wide association studies (GWAS) performed with these 3D traits identified numerous candidate genes, nine of which had been previously confirmed in the literature. This work provides a 3D phenomics solution tailored for slender organs and offers novel insights into the genetic regulation of complex morphological traits in rice. Full article
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15 pages, 236 KiB  
Article
Insights into Fanconi Anemia Based on Molecular and Clinical Characteristics: A Multicentre Study of 13 Patients
by Simoni Saranti, Nikoletta Selenti, Christalena Sofocleous, Joanne Traeger-Synodinos, Antonis Kattamis, Vassilios Papadakis, Evgenios Goussetis, Charikleia Kelaidi, Anna Paisiou, Sophia Polychronopoulou and Lydia Kossiva
Children 2025, 12(8), 973; https://doi.org/10.3390/children12080973 - 24 Jul 2025
Viewed by 328
Abstract
Background: Fanconi Anemia (FA) is a rare disorder, characterized by chromosomal instability, congenital abnormalities, progressive bone marrow failure, and predisposition to cancer. FA is caused by pathogenic variants in any of the 23 (FANCA-FANCY) linked genes. Procedure: Retrospective analysis [...] Read more.
Background: Fanconi Anemia (FA) is a rare disorder, characterized by chromosomal instability, congenital abnormalities, progressive bone marrow failure, and predisposition to cancer. FA is caused by pathogenic variants in any of the 23 (FANCA-FANCY) linked genes. Procedure: Retrospective analysis of 13 FA patients with a causative variant was performed. Patients (6 boys and 7 girls) aged from 9 to 26 years old, (mean age of 7.3 years), at diagnosis. Results: Phenotype evaluation demonstrated in 11/13 patients’ congenital anomalies, with pigmentary changes and short stature, present in 90% of cases. Hematological abnormalities were present in 10/11 patients, with thrombocytopenia being the prominent finding. Genetic analysis for the most common complementation group FA-A revealed that 12/13 patients belonged to this group and only one patient was found to be FA-E. Exon deletions, single nucleotide variations, and duplications were identified. Familial patterns, due to consanguinity, were evident in one case. Twelve patients underwent hematopoietic stem cell transplantation (HSCT), with variable pre-HSCT supportive treatments. Post-HSCT data showed that 9 out of 10 patients for whom follow up data was available, survived for a median time of 5.4 years. Complications like acute graft-versus-host disease were noted. Conclusions: Our study highlights the importance of genotype towards tailored monitoring for children and families with FA. Full article
(This article belongs to the Section Pediatric Hematology & Oncology)
17 pages, 2774 KiB  
Article
Chronic Morphine Treatment Leads to a Global DNA Hypomethylation via Active and Passive Demethylation Mechanisms in mESCs
by Manu Araolaza, Iraia Muñoa-Hoyos, Itziar Urizar-Arenaza, Irune Calzado and Nerea Subirán
Int. J. Mol. Sci. 2025, 26(15), 7056; https://doi.org/10.3390/ijms26157056 - 22 Jul 2025
Viewed by 260
Abstract
Epigenetic regulation, particularly DNA methylation, plays a crucial role in embryonic development by controlling gene expression patterns. The disruption of this regulation by environmental factors can have long-lasting consequences. Opioid drugs, such as morphine, are known to cross the placental barrier and affect [...] Read more.
Epigenetic regulation, particularly DNA methylation, plays a crucial role in embryonic development by controlling gene expression patterns. The disruption of this regulation by environmental factors can have long-lasting consequences. Opioid drugs, such as morphine, are known to cross the placental barrier and affect the developing central nervous system, yet their precise epigenetic effects during early development remain unclear. This study aimed to elucidate the impact of chronic morphine exposure on the DNA methylation landscape and gene expression in mouse embryonic stem cells (mESCs). mESCs were chronically exposed to morphine (10 μM for 24 h). Genome-wide bisulfite sequencing was performed to identify DNA methylation changes, while RNA sequencing (RNA-Seq) assessed corresponding gene expression alterations. Global levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) were quantified using mass spectrometry. Morphine exposure induced global DNA hypomethylation and identified 16,808 differentially methylated genes (DMGs) related to development, cell signalling, metabolism, and transcriptional regulation. Integrative transcriptomic analysis with RNA-Seq data revealed 651 overlapping genes, including alterations in key epigenetic regulators involved on DNA methylation machinery. Specifically, Tet1 was upregulated with promoter hypomethylation, while Dnmt1 was downregulated, without changes in promoter methylation after morphine exposiure. Mass spectrometry results confirmed a global decrease in 5mC levels alongside increased 5hmC, indicating the involvement of both passive and active demethylation pathways. These findings demonstrate for the first time that morphine disrupts the epigenetic homeostasis of mESCs by promoting global and gene-specific DNA demethylation, which might be key to the phenotypic changes that occur in adulthood. This work provides novel mechanistic insights into how opioid exposure during early development may lead to persistent epigenetic alterations, with potential long-term implications for neurodevelopment and disease susceptibility. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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20 pages, 3367 KiB  
Review
Intravascular Lymphoma: A Unique Pattern Underlying a Protean Disease
by Mario Della Mura, Joana Sorino, Filippo Emanuele Angiuli, Gerardo Cazzato, Francesco Gaudio and Giuseppe Ingravallo
Cancers 2025, 17(14), 2355; https://doi.org/10.3390/cancers17142355 - 15 Jul 2025
Viewed by 272
Abstract
Intravascular lymphoma (IVL) is a rare, aggressive subtype of non-Hodgkin lymphoma (NHL) characterized by the selective proliferation of neoplastic lymphoid cells within small and medium-sized blood vessels, most frequently of B-cell origin (IVLBCL). Its protean clinical presentation, lack of pathognomonic findings, and absence [...] Read more.
Intravascular lymphoma (IVL) is a rare, aggressive subtype of non-Hodgkin lymphoma (NHL) characterized by the selective proliferation of neoplastic lymphoid cells within small and medium-sized blood vessels, most frequently of B-cell origin (IVLBCL). Its protean clinical presentation, lack of pathognomonic findings, and absence of tumor masses or lymphadenopathies often lead to diagnostic delays and poor outcomes. IVLBCL can manifest in classic, hemophagocytic syndrome-associated (HPS), or cutaneous variants, with extremely variable organ involvement including the central nervous system (CNS), skin, lungs, and endocrine system. Diagnosis requires histopathologic identification of neoplastic intravascular lymphoid cells via targeted or random tissue biopsies. Tumor cells are highly atypical and display a non-GCB B-cell phenotype, often expressing CD20, MUM1, BCL2, and MYC; molecularly, they frequently harbor mutations in MYD88 and CD79B, defining a molecular profile shared with ABC-type DLBCL of immune-privileged sites. Therapeutic approaches are based on rituximab-containing chemotherapy regimens (R-CHOP), often supplemented with CNS-directed therapy due to the disease’s marked neurotropism. Emerging strategies include autologous stem cell transplantation (ASCT) and novel immunotherapeutic approaches, potentially exploiting the frequent expression of PD-L1 by tumor cells. A distinct but related entity, intravascular NK/T-cell lymphoma (IVNKTCL), is an exceedingly rare EBV-associated lymphoma, showing unique own histologic, immunophenotypic, and molecular features and an even poorer outcome. This review provides a comprehensive overview of the current understandings about clinicopathological, molecular, and therapeutic landscape of IVL, emphasizing the need for increased clinical awareness, standardized diagnostic protocols, and individualized treatment strategies for this aggressive yet intriguing malignancy. Full article
(This article belongs to the Special Issue Advances in Pathology of Lymphoma and Leukemia)
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13 pages, 2865 KiB  
Article
Fine Mapping of BrTCP1 as a Key Regulator of Branching in Flowering Chinese Cabbage (Brassica rapa subsp. chinensis)
by Chuanhong Liu, Xinghua Qi, Shuo Fu, Chao Zheng, Chao Wu, Xiaoyu Li, Yun Zhang and Xueling Ye
Horticulturae 2025, 11(7), 824; https://doi.org/10.3390/horticulturae11070824 - 10 Jul 2025
Viewed by 292
Abstract
Branching is a critical agronomic trait in flowering Chinese cabbage (Brassica rapa subsp. chinensis), influencing plant architecture and yield. In this study, there was a highly significant difference between CX010 (single primary rosette branches) and BCT18 (multiple primary rosette branches). Phenotypic [...] Read more.
Branching is a critical agronomic trait in flowering Chinese cabbage (Brassica rapa subsp. chinensis), influencing plant architecture and yield. In this study, there was a highly significant difference between CX010 (single primary rosette branches) and BCT18 (multiple primary rosette branches). Phenotypic analysis revealed significant differences in primary rosette branch numbers, with BCT18 showing up to 15 branches and CX010 displaying only one main stem branch. Genetic analysis indicated that branching was controlled by quantitative trait loci (QTL) with a normal distribution of branch numbers. Using bulked segregant analysis coupled with sequencing (BSA-seq), we identified a candidate interval of approximately 2.96 Mb on chromosome A07 linked to branching. Fine mapping narrowed this to a 172 kb region containing 29 genes, with BraA07g032600.3C (BrTCP1) as the most likely candidate. cDNA cloning of the BrTCP1 gene revealed several variations in BCT18 compared to CX010, including a 6 bp insertion, 10 SNPs, and two single-nucleotide deletions. Expression analysis indicated that BrTCP1 was highly expressed in the rosette stems of CX010 compared to BCT18, consistent with its role as a branching suppressor. The heterologous mutants in Arabidopsis confirmed the conserved role of BrTCP1 in branch inhibition. These findings reveal that BrTCP1 might be a key regulator of branching in flowering Chinese cabbage, providing insights into the molecular mechanisms underlying this trait and offering a framework for genetic improvement in Brassica crops. Full article
(This article belongs to the Special Issue Genetics and Molecular Breeding of Brassica Crops)
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