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Search Results (752)

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Keywords = coordination of Ca2+

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17 pages, 1306 KB  
Article
Hydrogeochemical Evolution and Ecological Irrigation Evaluation of Mine Water in an Arid Coal Region: A Case Study from Northwest China
by Hao Wang, Hongbo Shang, Tiantian Wang, Jiankun Xue, Xiaodong Wang, Zhenfang Zhou and Qiangmin Wang
Water 2025, 17(21), 3132; https://doi.org/10.3390/w17213132 (registering DOI) - 31 Oct 2025
Abstract
Investigating ecological irrigation risks associated with mine water utilization is of great significance for alleviating water resource shortages in arid mining regions of western China, thereby supporting efficient coal extraction and coordinated ecological development. In this study, a representative mining area in Xinjiang [...] Read more.
Investigating ecological irrigation risks associated with mine water utilization is of great significance for alleviating water resource shortages in arid mining regions of western China, thereby supporting efficient coal extraction and coordinated ecological development. In this study, a representative mining area in Xinjiang was investigated to reveal the evolution patterns of mine water quality under arid geo-environmental conditions in western China and to systematically assess environmental risks induced by ecological irrigation. Surface water, groundwater, and mine water samples were collected to study ion ratio coefficients, hydrochemical characteristics, and evolution processes. Based on this, a multi-index analysis was employed to evaluate ecological irrigation risks and establish corresponding risk control measures. The results show that the total dissolved solids (TDS) of mine water in the study area are all greater than 1000 mg/L. The evolution of mine water quality is mainly controlled by water–rock interaction and is affected by evaporation and concentration. The main ions Na+, Cl, Ca2+, and SO42− originate from the dissolution of halite, gypsum, and anorthite. If the mine water is directly used for irrigation without treatment, the soluble sodium content, sodium adsorption ratio, salinity hazard, and magnesium adsorption ratio will exceed the limits, leading to the accumulation of Na+ in the soil, affecting plant photosynthesis, and posing potential threats to the groundwater environment. Given the evolution process of mine water quality and the potential risks of direct use for irrigation, measures can be taken across three aspects: nanofiltration combined with reverse osmosis desalination, adoption of drip irrigation and intermittent irrigation technologies, and selection of drought-tolerant vegetation. These measures can reduce the salt content of mine water, decrease the salt accumulation in the soil layer, and lower the risk of groundwater pollution, thus reducing the environmental risks of ecological irrigation with mine water. The research will provide an important theoretical basis for the scientific utilization and management of mine water resources in arid areas by revealing the evolution law of mine water quality in arid areas and clarifying its ecological irrigation environmental risks. Full article
41 pages, 3718 KB  
Article
Behavioral Balance in Tryptophan Turmoil: Regional Metabolic Rewiring in Kynurenine Aminotransferase II Knockout Mice
by Ágnes Szabó, Zsolt Galla, Eleonóra Spekker, Diána Martos, Mónika Szűcs, Annamária Fejes-Szabó, Ágnes Fehér, Keiko Takeda, Kinuyo Ozaki, Hiromi Inoue, Sayo Yamamoto, Péter Monostori, József Toldi, Etsuro Ono, László Vécsei and Masaru Tanaka
Cells 2025, 14(21), 1711; https://doi.org/10.3390/cells14211711 (registering DOI) - 31 Oct 2025
Abstract
Background: Cognitive, emotional, and social impairments are pervasive across neuropsychiatric conditions, where alterations in the tryptophan (Trp)–kynurenine pathway and its product kynurenic acid (KYNA) from kynurenine aminotransferases (KATs) have been linked to Alzheimer’s disease, Parkinson’s disease, depression, and post-traumatic stress disorder. In novel [...] Read more.
Background: Cognitive, emotional, and social impairments are pervasive across neuropsychiatric conditions, where alterations in the tryptophan (Trp)–kynurenine pathway and its product kynurenic acid (KYNA) from kynurenine aminotransferases (KATs) have been linked to Alzheimer’s disease, Parkinson’s disease, depression, and post-traumatic stress disorder. In novel CRISPR/Cas9-engineered KAT II knockout (aadat−/− also known as kat2−/−) mice, we observed despair-linked depression-like behavior with peripheral excitotoxicity and oxidative stress. KAT II’s role and its crosstalk with serotonin, indole-pyruvate, and tyrosine–dopamine remain unclear. It is unknown whether deficits extend to cognitive, emotional, motor, and social domains or whether brain tissues mirror peripheral stress. Objectives: Delineate domain-wide behaviors, brain oxidative/excitotoxic profiles, and pathway interactions attributable to KAT II. Results: Behavior was unchanged across strains. kat2−/− deletion remodeled Trp metabolic pathways: 3-hydroxykynurenine increased, xanthurenic acid decreased, KYNA fell in cortex and hippocampus but rose in striatum, quinaldic acid decreased in cerebellum and brainstem. These region-specific changes indicate metabolic stress across the brain and align with higher oxidative load and signs of excitotoxic pressure. Conclusions: Here, we show that KAT II deletion reshapes regional Trp metabolism and amplifies oxidative and excitotoxic imbalance. Although domain-wide behavioral measures, spanning cognition, sociability, and motor coordination, remained largely unchanged, these neurochemical alterations signify a latent emotional bias rather than overt depressive-like behavior. This work, therefore, refines prior findings by delineating KAT II–linked biochemical vulnerability as a potential substrate for stress-reactive affective dysregulation. Full article
32 pages, 11840 KB  
Article
Long-Term Spatiotemporal Relationship of Urban–Rural Gradient Between Land Surface Temperature and Nighttime Light in Representative Cities Across China’s Climate Zones
by Juanzhu Liang, Wenfang Li, Yuke Zhou, Xueyang Han and Daqing Li
Remote Sens. 2025, 17(21), 3585; https://doi.org/10.3390/rs17213585 - 30 Oct 2025
Viewed by 44
Abstract
In the context of rapid urbanization, human activities have profoundly transformed urban thermal environments. However, most existing studies have focused on single cities or relatively uniform climatic contexts, and the long-term dynamics between land surface temperature (LST) and nighttime light (NTL) across urban–rural [...] Read more.
In the context of rapid urbanization, human activities have profoundly transformed urban thermal environments. However, most existing studies have focused on single cities or relatively uniform climatic contexts, and the long-term dynamics between land surface temperature (LST) and nighttime light (NTL) across urban–rural gradients in diverse climates remain insufficiently explored. This gap limits a systematic understanding of how human activities and thermal environments co-evolve under varying regional conditions. To address this gap, we selected ten representative cities spanning multiple climate zones in China. Using MODIS LST and NTL datasets from 2000 to 2020, we developed an urban–rural gradient analysis framework to systematically assess the spatiotemporal response patterns and coupling mechanisms between LST and NTL. Our findings reveal the following: (1) From 2000 to 2020, NTL exhibited a pronounced upward trend across all climate zones, most notably in the marginal tropical humid region, while LST changes were relatively moderate. (2) LST and NTL displayed power-law distributions along urban–rural transects, marked by steep declines in monocentric cities and gradual transitions in polycentric cities, with sharper thermal gradients in northern and inland areas and more gradual transitions in southern and coastal regions. (3) The long-term increase in NTL was most evident in suburban areas (0.94 nW/cm2/sr/a), surpassing that in urban cores (0.68 nW/cm2/sr/a) and rural zones (0.60 nW/cm2/sr/a), with inland cities (0.84 nW/cm2/sr/a) outpacing their coastal counterparts. Although LST changes were modest, suburban warming (0.16 ± 0.08 °C/a) was over twice that of urban and rural areas. Notably, the synergistic escalation of light and heat was most pronounced in tropical and subtropical cities. (4) Eastern coastal cities exhibited strongly synchronized rises in NTL and LST, whereas cities in the plateau, temperate semi-arid, and mid-temperate arid regions showed clear decoupling. Along urban–rural gradients, NTL–LST correlations generally weakened from urban centers to peripheries, yet coupling coordination peaked in fringe areas (mean = 0.63), underscoring pronounced spatial heterogeneity. This study advances our understanding of the spatiotemporal coupling of urban light and heat under varying climatic and urbanization contexts, offering critical insights into managing urban thermal environments. Full article
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20 pages, 7297 KB  
Article
Student Classroom Behavior Recognition Based on YOLOv8 and Attention Mechanism
by Jingpu Zhang, Lizheng Guo and Xuyang Wang
Information 2025, 16(11), 934; https://doi.org/10.3390/info16110934 - 27 Oct 2025
Viewed by 364
Abstract
Accurately recognizing student classroom behaviors is essential for analyzing teacher–student interactions and enabling intelligent educational assessment. Although deep learning offers promising solutions, existing methods often perform poorly in complex classroom environments due to occlusions and subtle, overlapping actions. To address these issues, this [...] Read more.
Accurately recognizing student classroom behaviors is essential for analyzing teacher–student interactions and enabling intelligent educational assessment. Although deep learning offers promising solutions, existing methods often perform poorly in complex classroom environments due to occlusions and subtle, overlapping actions. To address these issues, this article proposes a robust and efficient method for behavior recognition by enhancing the You Only Look Once version 8 (YOLOv8) architecture with a Multi-Head Self-Attention (MHSA) module, termed YOLOv8-MHSA. The integration of MHSA allows the model to capture contextual relationships between distant spatial features, which is critical for distinguishing similar behaviors. For a comprehensive evaluation, we also implement a model with Coordinate Attention (CA). Experimental results on a standard dataset demonstrate the superiority of our YOLOv8-MHSA model, which achieves a precision of 0.86, recall of 0.807, mAP50 of 0.855, and mAP50-95 of 0.677, delivering competitive performance compared to the state-of-the-art SBD-Net. These findings validate that explicit contextual modeling via self-attention significantly boosts performance in fine-grained behavior recognition. Consequently, this research has direct potential applications in providing automated, data-driven tools for teacher training, classroom quality assessment, and, ultimately, supporting the development of personalized education systems. Full article
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21 pages, 2519 KB  
Article
Efficient Lightweight Image Classification via Coordinate Attention and Channel Pruning for Resource-Constrained Systems
by Yao-Liang Chung
Future Internet 2025, 17(11), 489; https://doi.org/10.3390/fi17110489 - 25 Oct 2025
Viewed by 307
Abstract
Image classification is central to computer vision, supporting applications from autonomous driving to medical imaging, yet state-of-the-art convolutional neural networks remain constrained by heavy floating-point operations (FLOPs) and parameter counts on edge devices. To address this accuracy–efficiency trade-off, we propose a unified lightweight [...] Read more.
Image classification is central to computer vision, supporting applications from autonomous driving to medical imaging, yet state-of-the-art convolutional neural networks remain constrained by heavy floating-point operations (FLOPs) and parameter counts on edge devices. To address this accuracy–efficiency trade-off, we propose a unified lightweight framework built on a pruning-aware coordinate attention block (PACB). PACB integrates coordinate attention (CA) with L1-regularized channel pruning, enriching feature representation while enabling structured compression. Applied to MobileNetV3 and RepVGG, the framework achieves substantial efficiency gains. On GTSRB, MobileNetV3 parameters drop from 16.239 M to 9.871 M (–6.37 M) and FLOPs from 11.297 M to 8.552 M (–24.3%), with accuracy improving from 97.09% to 97.37%. For RepVGG, parameters fall from 7.683 M to 7.093 M (–0.59 M) and FLOPs from 31.264 M to 27.918 M (–3.35 M), with only ~0.51% average accuracy loss across CIFAR-10, Fashion-MNIST, and GTSRB. Complexity analysis further confirms PACB does not increase asymptotic order, since the additional CA operations contribute only lightweight lower-order terms. These results demonstrate that coupling CA with structured pruning yields a scalable accuracy–efficiency trade-off under hardware-agnostic metrics, making PACB a promising, deployment-ready solution for mobile and edge applications. Full article
(This article belongs to the Special Issue Clustered Federated Learning for Networks)
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20 pages, 5128 KB  
Article
Bioinformatics Approach to mTOR Signaling Pathway-Associated Genes and Cancer Etiopathogenesis
by Kursat Ozdilli, Gozde Oztan, Demet Kıvanç, Ruştu Oğuz, Fatma Oguz and Hayriye Senturk Ciftci
Genes 2025, 16(11), 1253; https://doi.org/10.3390/genes16111253 - 24 Oct 2025
Viewed by 338
Abstract
Background/Objectives: The mTOR serine/threonine kinase coordinates protein translation, cell growth, and metabolism, and its dysregulation promotes tumorigenesis. We present a reproducible, pan-cancer, network-aware framework that integrates curated resources with genomics to move beyond pathway curation, yielding falsifiable hypotheses and prioritized candidates for [...] Read more.
Background/Objectives: The mTOR serine/threonine kinase coordinates protein translation, cell growth, and metabolism, and its dysregulation promotes tumorigenesis. We present a reproducible, pan-cancer, network-aware framework that integrates curated resources with genomics to move beyond pathway curation, yielding falsifiable hypotheses and prioritized candidates for mTOR axis biomarker validation. Materials and Methods: We assembled MTOR-related genes and interactions from GeneCards, KEGG, STRING, UniProt, and PathCards and harmonized identifiers. We formulated a concise working model linking genotype → pathway architecture (mTORC1/2) → expression-level rewiring → phenotype. Three analyses operationalized this model: (i) pan-cancer alteration mapping to separate widely shared drivers from tumor-specific nodes; (ii) expression-based activity scoring to quantify translational/nutrient-sensing modules; and (iii) topology-aware network propagation (personalized PageRank/Random Walk with Restart on a high-confidence STRING graph) to nominate functionally proximal neighbors. Reproducibility was supported by degree-normalized diffusion, predefined statistical thresholds, and sensitivity analyses. Results: Gene ontology analysis demonstrated significant enrichment for mTOR-related processes (TOR/TORC1 signaling and cellular responses to amino acids). Database synthesis corroborated disease associations involving MTOR and its partners (e.g., TSC2, RICTOR, RPTOR, MLST8, AKT1 across selected carcinomas). Across cohorts, our framework distinguishes broadly shared upstream drivers (PTEN, PIK3CA) from lineage-enriched nodes (e.g., RICTOR-linked components) and prioritizes non-mutated, network-proximal candidates that align with mTOR activity signatures. Conclusions: This study delivers a transparent, pan-cancer framework that unifies curated biology, genomics, and network topology to produce testable predictions about the mTOR axis. By distinguishing shared drivers from tumor-specific nodes and elevating non-mutated, topology-inferred candidates, the approach refines biomarker discovery and suggests architecture-aware therapeutic strategies. The analysis is reproducible and extensible, supporting prospective validation of prioritized candidates and the design of correlative studies that align pathway activity with clinical response. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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24 pages, 3969 KB  
Article
Icing Detection of Wind Turbine Blades Based on an Improved PP-YOLOE Detection Network
by Zhangzhuo Sun, Jiangbo Qian, Ao Liu, Shangyun Yao, Xinzhu Lv and Liwei Shao
Sensors 2025, 25(20), 6438; https://doi.org/10.3390/s25206438 - 17 Oct 2025
Viewed by 409
Abstract
In cold and highly humid regions, wind turbine blades (WTB) are susceptible to icing, which can have a significant impact on the security and economic operation of turbines. Therefore, precise and prompt icing status detection is pivotal for maintaining wind turbine operational normalcy. [...] Read more.
In cold and highly humid regions, wind turbine blades (WTB) are susceptible to icing, which can have a significant impact on the security and economic operation of turbines. Therefore, precise and prompt icing status detection is pivotal for maintaining wind turbine operational normalcy. In this research, an improved PP-YOLOE network is developed for classifying and detecting the icing state of WTB. First, a dataset of WTB icing is constructed based on a wind tunnel laboratory and expanded to improve the generalization of the model. To enhance feature representation, the network architecture was improved by embedding a coordinate attention (CA) mechanism and integrating atrous spatial pyramid pooling (ASPP) to better capture multi-scale contextual information. Moreover, a key innovation of this work is the novel application of a particle swarm optimization (PSO) algorithm to systematically automate hyperparameter tuning. Through ablation experiments and comparative tests, the improved PP-YOLOE network demonstrates superior overall performance on this dataset, achieving a multiple average precision of 0.94. It surpasses the original model across multiple evaluation metrics, indicating a robust and meaningful enhancement. The improved PP-YOLOE network proposed in this study provides a promising and effective method for WTB icing detection. This work provides a paradigm for applying advanced deep learning techniques to enhance intelligent industrial inspection tasks. Full article
(This article belongs to the Section Intelligent Sensors)
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15 pages, 10808 KB  
Article
Kdm7aa Orchestrates an Immunomodulatory Cardiomyocyte Program to Enable Zebrafish Heart Regeneration
by Weibin Lin, Yuan Shi, Jin Tian, Xinru Liu, Fubin Weng and Zekai Wu
Int. J. Mol. Sci. 2025, 26(20), 10044; https://doi.org/10.3390/ijms262010044 - 15 Oct 2025
Viewed by 231
Abstract
Myocardial infarction triggers limited repair in adult mammals but robust regeneration in zebrafish. Epigenetic regulation and immune responses are recognized as critical for successful regeneration. However, the molecular links between these processes have not been fully elucidated. By performing single-cell RNA sequencing of [...] Read more.
Myocardial infarction triggers limited repair in adult mammals but robust regeneration in zebrafish. Epigenetic regulation and immune responses are recognized as critical for successful regeneration. However, the molecular links between these processes have not been fully elucidated. By performing single-cell RNA sequencing of zebrafish ventricular cardiomyocytes after injury, we identified a regeneration-induced immunomodulatory cluster that specifically expressed the histone demethylase gene kdm7aa. Functional perturbations, including CRISPR/Cas9-mediated kdm7aa mutation and pharmacological inhibition of Kdm7aa activity using TC-E5002, impaired cardiac regeneration. Bulk RNA sequencing showed that kdm7aa drives an inflammatory transcriptional program, prominently activating chemokines such as cxcl8a and cxcl19 that coordinate immune cell recruitment. Cross-species analyses revealed injury-induced Kdm7a upregulation in regeneration-competent neonatal mouse hearts but not in adult mouse or human hearts. These data identified Kdm7aa as a regeneration-induced epigenetic regulator that enabled cardiomyocytes to adopt a transient immune-activating phenotype, linking histone demethylation to chemokine signaling and suggesting a potential therapeutic strategy to enhance mammalian cardiac repair. Full article
(This article belongs to the Section Molecular Immunology)
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23 pages, 3542 KB  
Article
Modulation of Nuclear Factor Kappa B Signaling and microRNA Profiles by Adalimumab in LPS-Stimulated Keratinocytes
by Aleksandra Plata-Babula, Wojciech Kulej, Paweł Ordon, Julia Gajdeczka, Martyna Stefaniak, Artur Chwalba, Piotr Gościniewicz, Tomasz Kulpok and Beniamin Oskar Grabarek
Int. J. Mol. Sci. 2025, 26(20), 10035; https://doi.org/10.3390/ijms262010035 - 15 Oct 2025
Viewed by 242
Abstract
Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperactivation and dysregulated cytokine signaling, with nuclear factor kappa B (NF-κB), a master transcription factor that regulates immune and inflammatory gene expression, playing a central role. Adalimumab, a monoclonal antibody that inhibits tumor [...] Read more.
Psoriasis is a chronic inflammatory skin disease characterized by keratinocyte hyperactivation and dysregulated cytokine signaling, with nuclear factor kappa B (NF-κB), a master transcription factor that regulates immune and inflammatory gene expression, playing a central role. Adalimumab, a monoclonal antibody that inhibits tumor necrosis factor alpha (TNF-α), is widely used in psoriasis therapy, yet its molecular effects on NF-κB-associated genes and microRNAs (miRNAs) in keratinocytes remain insufficiently defined. In this study, immortalized human keratinocytes (HaCaT cells) were exposed to lipopolysaccharide (LPS) to induce inflammatory stress and treated with adalimumab for 2, 8, and 24 h. Transcriptome-wide profiling was performed using messenger RNA (mRNA) and miRNA microarrays, followed by validation with reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Bioinformatic analyses included prediction of miRNA–mRNA interactions, construction of protein–protein interaction (PPI) networks, and gene ontology (GO) enrichment. Adalimumab reversed LPS-induced upregulation of NF-κB-associated genes, including inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB), interleukin-1 receptor-associated kinase 1 (IRAK1), TNF receptor-associated factor 2 (TRAF2), mitogen-activated protein kinase kinase kinase 7 (MAP3K7), and TNF alpha-induced protein 3 (TNFAIP3), with concordant changes observed at the protein level. Several regulatory miRNAs, notably miR-1297, miR-30a, miR-95-5p, miR-125b, and miR-4329, showed reciprocal expression changes consistent with anti-inflammatory activity. STRING analysis identified IKBKB as a central hub in the PPI network, while GO enrichment highlighted immune regulation, apoptosis, and NF-κB signaling. These findings demonstrate that adalimumab modulates NF-κB activity in keratinocytes through coordinated regulation of gene, protein, and miRNA expression, providing mechanistic insight into TNF-α blockade in psoriasis. Full article
(This article belongs to the Collection Advances in Cell and Molecular Biology)
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15 pages, 4217 KB  
Article
TaCML49-B, a Calmodulin-like Protein, Interacts with TaIQD23 to Positively Regulate Salt Tolerance in Wheat
by Jingna Ru, Jiamin Hao, Bingqing Hao, Xiaoqian Ji, Jiale Yang, Hongtao Wang, Baoquan Quan, Pengyan Guo, Jiping Zhao, Huawei Shi and Zhaoshi Xu
Plants 2025, 14(20), 3163; https://doi.org/10.3390/plants14203163 - 15 Oct 2025
Viewed by 291
Abstract
Calcium signaling is essential for coordinating plant responses to diverse stimuli and regulating growth and development. Among calcium sensors, calmodulin (CaM) and CaM-like proteins (CMLs) represent a class that, despite increasing research, remains incompletely characterized in wheat, with many interacting partners and biological [...] Read more.
Calcium signaling is essential for coordinating plant responses to diverse stimuli and regulating growth and development. Among calcium sensors, calmodulin (CaM) and CaM-like proteins (CMLs) represent a class that, despite increasing research, remains incompletely characterized in wheat, with many interacting partners and biological functions remaining largely elusive. This study conducted bioinformatics analyses of subgroup II CaM/CMLs, characterizing their phylogenetic relationships, conserved motifs, sequence features, and cis-elements. Expression analysis revealed that TaCML49-B was significantly upregulated in roots under salt stress. Moreover, TaCML49-B was localized to nucleus, cytoplasm, and membrane. Function characterization demonstrated that overexpression of TaCML49-B in Arabidopsis enhanced salt tolerance, whereas the BSMV-VIGS silencing of TaCML49-B reduced salt resistance in wheat. Furthermore, STRING database prediction analysis and bimolecular fluorescence complementation (BiFC) assay confirmed that TaCML49-B can physically interact with TaIQD23, which encodes an IQ67 domain protein, suggesting its potential involvement in the salt stress signaling pathway. Collectively, our findings indicate that TaCML49-B functions as a positive role in wheat salt stress response, thereby providing novel insights into the functions of TaCML genes and calcium signaling in wheat. Full article
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38 pages, 1914 KB  
Review
Photobiomodulation Meets Mechanotransduction: Immune-Stromal Crosstalk in Orthodontic Remodeling
by Jovan Marković and Miodrag Čolić
Biomedicines 2025, 13(10), 2495; https://doi.org/10.3390/biomedicines13102495 - 13 Oct 2025
Viewed by 748
Abstract
Orthodontic tooth movement (OTM) arises from force-induced mechanotransduction within the periodontal ligament (PDL), which coordinates osteoblast and osteoclast activity with immune responses to remodel the PDL and alveolar bone. This review integrates contemporary biological insights on OTM and assesses photobiomodulation (PBM) as an [...] Read more.
Orthodontic tooth movement (OTM) arises from force-induced mechanotransduction within the periodontal ligament (PDL), which coordinates osteoblast and osteoclast activity with immune responses to remodel the PDL and alveolar bone. This review integrates contemporary biological insights on OTM and assesses photobiomodulation (PBM) as an adjunctive therapy. We propose that mechanical and photonic inputs may interact and potentiate signaling through the Ca2+-NFAT, MAPK (ERK, p38, JNK), PI3K–Akt–mTOR, NF-kB, TGF-β/Smad, and Wnt/β-catenin pathways. Such interaction could influence processes such as cell proliferation, differentiation, specific cellular functions, apoptosis, autophagy, and communication between stromal and immune cells. This convergence establishes a solid foundation for understanding the context-dependent effects of PBM in OTM. In principle, PBM appears most effective as a phase-tuned adjunct, promoting early inflammatory recruitment of osteoclasts and subsequently facilitating late-phase remodeling through immunomodulatory and reparative mechanisms. However, inconsistent irradiation parameters, small sample sizes, trial heterogeneity, and the absence of mechanistic endpoints undermine current conclusions. Furthermore, the lack of integrated PBM–OTM models limits mechanistic understanding, as much of the available evidence is derived from non-OTM contexts. Overall, PBM remains a promising adjunct in orthodontics, with the potential to integrate mechanical and photonic signals in a phase-dependent manner, though its application is not yet standardized. Full article
(This article belongs to the Section Cell Biology and Pathology)
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27 pages, 6020 KB  
Article
Engineered Nanobody-Bearing Extracellular Vesicles Enable Precision Trop2 Knockdown in Resistant Breast Cancer
by Jassy Mary S. Lazarte, Mounika Aare, Sandeep Chary Padakanti, Arvind Bagde, Aakash Nathani, Zachary Meeks, Li Sun, Yan Li and Mandip Singh
Pharmaceutics 2025, 17(10), 1318; https://doi.org/10.3390/pharmaceutics17101318 - 11 Oct 2025
Viewed by 554
Abstract
Background/Objectives: Trophoblast cell surface antigen 2 (Trop2), a transmembrane glycoprotein overexpressed in a broad spectrum of epithelial malignancies but minimally expressed in normal tissues, has emerged as a clinically relevant prognostic biomarker and therapeutic target, particularly in breast cancer. This study aims [...] Read more.
Background/Objectives: Trophoblast cell surface antigen 2 (Trop2), a transmembrane glycoprotein overexpressed in a broad spectrum of epithelial malignancies but minimally expressed in normal tissues, has emerged as a clinically relevant prognostic biomarker and therapeutic target, particularly in breast cancer. This study aims to develop an enhanced way of targeting Trop2 expression in tumors and blocking it using extracellular vesicles (EVs) bioengineered to express a nanobody sequence against Trop2 (NB60 E). Methods: Here, a plasmid construct was designed to express the Trop2 sequence, NB60, flanked with HA tag and myc epitope and a PDGFR transmembrane domain in the C-terminal region, and was transfected into HEK293T cells for EVs isolation. The potency of NB60 E to knock down Trop2 in letrozole-resistant breast cancer cells (LTLT-Ca and MDA-MB-468 cells) was initially investigated. Thereafter, the effects of NB60 E on the cell viability and downstream signaling pathway of Trop2 via MTT assay and Western blotting were determined. Lastly, we also examined whether NB60 E treatment in Jurkat T cells affects IL-6, TNF-α, and IL-2 cytokine production by enzyme-linked immunosorbent assay (ELISA). Results: Results revealed treatment with NB60 E significantly reduced surface Trop2 expression across both cell lines by 23.5 ± 1.5% in MDA-MB-468, and 61.5 ± 1.5% in LTLT-Ca, relative to the HEK293T-derived control EVs (HEK293T E). NB60 E treatment resulted in a marked reduction in LTLT-Ca cell viability by 52.8 ± 0.9% at 48 h post-treatment. This was accompanied by downregulation of key oncogenic signaling molecules: phosphorylated ERK1/2 (p-ERK 1/2) decreased by 30 ± 4%, cyclin D1 by 67 ± 11%, phosphorylated STAT3 (p-STAT3) by 71.8 ± 1.6%, and vimentin by 40.8 ± 1.4%. ELISA analysis revealed significant decreases in IL-6 (−57.5 ± 1.5%, 7.4 ± 0.35 pg/mL) and TNF-α (−32.1 ± 0.3%, 6.1 ± 1.2 pg/mL) levels, coordinated by an increase in IL-2 secretion (22.1 ± 2.7%, 49.2 ± 1.1 pg/mL). Quantitative analysis showed marked reductions in the number of nodes (−45 ± 4.4%), junctions (−55 ± 3.5%), and branch points (−38 ± 1.2%), indicating suppression of angiogenic capacity. In vivo experiment using near-infrared Cy7 imaging demonstrated rapid and tumor-selective accumulation of NB60 E within 4 h post-administration, followed by efficient systemic clearance by 24 h. The in vivo results demonstrate the effectiveness of NB60 E in targeting Trop2-enriched tumors while being efficiently cleared from the system, thus minimizing off-target interactions with normal cells. Lastly, Trop2 expression in LTLT-Ca tumor xenografts revealed a significant reduction of 41.0 ± 4% following NB60 E treatment, confirming efficient targeted delivery. Conclusions: We present a first-in-field NB60 E-grafted EV therapy that precisely homes to Trop2-enriched breast cancers, silences multiple growth-and-invasion pathways, blocks angiogenesis, and rewires cytokine crosstalk, achieving potent antitumor effects with self-clearing, biomimetic carriers. Our results here show promising potential for the use of NB60 E as anti-cancer agents, not only for letrozole-resistant breast cancer but also for other Trop2-expressing cancers. Full article
(This article belongs to the Special Issue Extracellular Vesicles for Targeted Delivery)
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16 pages, 3467 KB  
Article
Coordination-Driven Rare Earth Fractionation in Kuliokite-(Y), (Y,HREE)4Al(SiO4)2(OH)2F5: A Crystal–Chemical Study
by Sergey V. Krivovichev, Victor N. Yakovenchuk, Olga F. Goychuk and Yakov A. Pakhomovsky
Minerals 2025, 15(10), 1064; https://doi.org/10.3390/min15101064 - 10 Oct 2025
Viewed by 215
Abstract
The crystal structure of kuliokite-(Y), Y4Al(SiO4)2(OH)2F5, has been re-investigated using the material from the type locality the Ploskaya Mt, Kola peninsula, Russian Arctic. It has been shown that in contrast to previous studies, [...] Read more.
The crystal structure of kuliokite-(Y), Y4Al(SiO4)2(OH)2F5, has been re-investigated using the material from the type locality the Ploskaya Mt, Kola peninsula, Russian Arctic. It has been shown that in contrast to previous studies, the mineral is monoclinic, Im, with a = 4.3213(1), b = 14.8123(6), c = 8.6857(3) Å, β = 102.872(4)°, and V = 541.99(3) Å3. The crystal structure was solved and refined to R1 = 0.030 on the basis of 3202 unique observed reflections. The average chemical composition determined by electron microprobe analysis is (Y2.96Yb0.49Er0.27Dy0.13Tm0.07Lu0.05Ho0.05Gd0.01Ca0.01)Σ4.04Al0.92Si2.04O8-[(OH)2.61F4.42]Σ7.03; the idealized formula is (Y,Yb,Er)4Al[SiO4]2(OH)2.5F4.5. The crystal structure of kuliokite-(Y) contains two symmetrically independent Y sites, Y1 and Y2, coordinated by eight and seven X anions, respectively (X = O, F). The coordination polyhedra can be described as a distorted square antiprism and a distorted pentagonal bipyramid, respectively. The refinement of site occupancies indicated that the mineral represents a rare case of HREE fractionation among two cation sites driven by their coordination numbers and geometry. In agreement with the lanthanide contraction, HREEs are selectively incorporated into the Y2 site with a smaller coordination number and tighter coordination environment. The strongest building unit of the structure is the [AlX2(SiO4)2] chain of corner-sharing AlX6 octahedra and SiO4 tetrahedra running along the a axis. The chains have their planes oriented parallel to (001). The Y atoms are located in between the chains, along with the F and (OH) anions, providing the three-dimensional integrity of the crystal structure. Each F anion is coordinated by three Y3+ cations to form planar (FY3)8+ triangles parallel to the (010) plane. The triangles share common edges to form [F2Y2]4+ chains parallel to the a axis. The analysis of second-neighbor coordination of Y sites allowed us to identify the structural topology of kuliokite-(Y) as the only case of the skd network in inorganic compounds, previously known in molecular structures only. The variety of anionic content in the mineral allows us to identify the potential existence of two other mineral species that can tentatively be named ‘fluorokuliokite-(Y)’ and ‘hydroxykuliokite-(Y)’. Full article
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23 pages, 9747 KB  
Article
Classification of Calcium-Dependent Protein Kinases and Their Transcriptional Response to Abiotic Stresses in Halophyte Nitraria sibirica
by Lu Lu, Ting Chen, Tiangui Yang, Chunxia Han, Jingbo Zhang, Jinhui Chen and Tielong Cheng
Plants 2025, 14(19), 3091; https://doi.org/10.3390/plants14193091 - 7 Oct 2025
Viewed by 366
Abstract
Calcium-dependent protein kinases (CDPKs) are key Ca2+ sensors in plants, mediating responses to abiotic stresses via phosphorylation signaling. In the halophyte Nitraria sibirica, which thrives in saline soils, we identified 19 CDPK genes (NsCDPKs) and classified them into four [...] Read more.
Calcium-dependent protein kinases (CDPKs) are key Ca2+ sensors in plants, mediating responses to abiotic stresses via phosphorylation signaling. In the halophyte Nitraria sibirica, which thrives in saline soils, we identified 19 CDPK genes (NsCDPKs) and classified them into four canonical angiosperm clades, highlighting conserved functional modules. Promoter analysis revealed diverse cis-acting elements responsive to light, hormones (ABA, MeJA, auxin, GA, SA), and abiotic stresses (drought, cold, wounding), along with numerous MYB binding sites, suggesting complex transcriptional regulation. Transcriptome profiling under salt stress (100 and 400 mM NaCl) showed induction of most NsCDPKs, with several genes significantly upregulated in roots and stems, indicating coordinated whole-plant activation. These salt-responsive NsCDPKs were also upregulated by cold but repressed under PEG-simulated drought, indicating stress-specific regulatory patterns. Fifteen MYB transcription factors, differentially expressed under salt stress, were predicted to interact with NsCDPK promoters, implicating them as upstream regulators. This study identified a potential salt- and cold-responsive CDPK regulatory module and a MYB-mediated transcriptional hierarchy in N. sibirica, providing insights into the molecular mechanisms of salinity adaptation and highlighting candidate genes that could be explored for improving salt tolerance in crop species. Full article
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14 pages, 1955 KB  
Article
Investigation of Photorecoordination Kinetics for Complexes of Bis(aza-18-crown-6)-Containing Dienones with Alkali and Alkaline-Earth Metal Cations via Time-Resolved Absorption Spectroscopy: Structure vs. Properties
by Oleg A. Alatortsev, Valeriy V. Volchkov, Mikhail N. Khimich, Ivan D. Sorokin, Mikhail Ya. Melnikov, Fedor E. Gostev, Ivan V. Shelaev, Victor A. Nadtochenko, Marina V. Fomina and Sergey P. Gromov
Molecules 2025, 30(19), 4005; https://doi.org/10.3390/molecules30194005 - 7 Oct 2025
Viewed by 369
Abstract
The analysis of time-resolved S1–Sn absorption spectra in the 0–500 ps range, together with quantum-chemical calculations, uncovered a photorecoordination reaction for the following complexes of CD6 (a bis(aza-18-crown-6)-containing dienone (ketocyanine dye) with a central cyclohexanone fragment): CD6·(Mn+)2 [...] Read more.
The analysis of time-resolved S1–Sn absorption spectra in the 0–500 ps range, together with quantum-chemical calculations, uncovered a photorecoordination reaction for the following complexes of CD6 (a bis(aza-18-crown-6)-containing dienone (ketocyanine dye) with a central cyclohexanone fragment): CD6·(Mn+)2 (M = Ba2+, Sr2+, Ca2+, K+). This process takes place over hundreds of fs and involves an “axial-to-equatorial” conformational change, with the solvation shell undergoing rearrangement as well. The characteristic photorecoordination times were found to correlate with the stability constants of the complexes. The lifetimes for the fluorescent states of CD6 and its complexes, namely CD6·(Mn+)2 (M = Ba2+, Sr2+, Ca2+, K+), are different; ergo, there is no photoejection of crowned cations into the solution. The calculated conformational profiles in the ground and excited states indicate the presence of an energy barrier in this process. A general photorelaxation pathway is suggested for CD6·(Mn+)2 metal complexes (M = Ba2+, Sr2+, Ca2+, K+). The coordination of cations via the carbonyl moiety in the dye molecule promotes photorecoordination of metal cations in the cavities of the azacrown ether fragment. Photorecoordination times were found to correlate with the degree of conjugation between the lone pairs in the N atoms of the aza-18-crown-6 ether and the π subsystem in the dye molecules (established for the CD4–CD6 metal–dye complex series, where CD4 and CD5 are related dyes with central cyclobutanone and cyclopentanone fragments, respectively). Full article
(This article belongs to the Section Macromolecular Chemistry)
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