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25 pages, 23171 KB  
Article
The Integrated Spatial Ecological Risk Assessment of Heavy-Metal Contamination in Arid Mining-Influenced Region in Central Asia
by Azamat Madibekov, Alibek Karimov, Laura Ismukhanova, Christian Opp, Askhat Zhadi, Botakoz Sultanbekova and Nurbek Tenirberdiev
Earth 2026, 7(5), 147; https://doi.org/10.3390/earth7050147 - 7 Sep 2026
Abstract
The spatial distributions of the potential ecological risk index (RI) and the geoaccumulation index (Igeo) in soils of the Zhetysu region (Kazakhstan) were examined. The enrichment factor ranged from 39.4 for cadmium to 21,481 for nickel. There are few non-ferrous metal enterprises and [...] Read more.
The spatial distributions of the potential ecological risk index (RI) and the geoaccumulation index (Igeo) in soils of the Zhetysu region (Kazakhstan) were examined. The enrichment factor ranged from 39.4 for cadmium to 21,481 for nickel. There are few non-ferrous metal enterprises and mineral deposits located in the region. Soil sampling was conducted at 54 locations across the region. The contamination indices were calculated based on the concentrations of four heavy metals in the soil in 2025: copper (Cu), lead (Pb), cadmium (Cd), and nickel (Ni). The RI index varied across the study area within range of 53–353, with an average value of 129. The main points of high environmental risk are the Balkhash Lake’s eastern coast (RI = 318) and industrial city Tekeli (RI = 353). The Igeo values were as follows: Cu −0.61–3.82 (mean: 2.07); Pb −0.58–3.35 (mean: 0.49); Cd −2.91–2.15 (mean: −0.11); and Ni −4.23–4.17 (mean: 0.43). The transport of contaminants occurs under the influence of the wind regime and water erosion processes. Lead, cadmium, and nickel have a variation coefficient greater than 50, indicating metal particle transport from adjacent areas. Wind patterns in certain areas of the region determine the distribution of foci of high heavy-metal concentrations in the soil. Full article
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21 pages, 3473 KB  
Article
Protein Expression Dynamics in Breast Cancer Cells Exposed to Nano-Encapsulated Tarin, the Taro Lectin
by Raiane V. Cardoso, Patricia R. Pereira, Cyntia S. Freitas, Yuri P. Souza, Dário E. Kalume, Giovani Carlo Verissimo da Costa, Carlos A. Conte-Junior and Vania Margaret Flosi Paschoalin
Pharmaceutics 2026, 18(9), 1123; https://doi.org/10.3390/pharmaceutics18091123 - 7 Sep 2026
Abstract
Background/Objectives: Tarin exhibits immunomodulatory and antiproliferative properties against several tumor cell lines. Nano-encapsulation in liposomes enhances its therapeutic potential by improving protein stability, bioavailability, and sustained release. Previous studies demonstrated that nano-encapsulated tarin induces cell cycle arrest, migration inhibition, apoptosis, and autophagy in [...] Read more.
Background/Objectives: Tarin exhibits immunomodulatory and antiproliferative properties against several tumor cell lines. Nano-encapsulation in liposomes enhances its therapeutic potential by improving protein stability, bioavailability, and sustained release. Previous studies demonstrated that nano-encapsulated tarin induces cell cycle arrest, migration inhibition, apoptosis, and autophagy in triple-negative breast cancer cells; however, the molecular mechanisms underlying these effects remain poorly understood. To investigate the proteomic response elicited by nano-encapsulated tarin, MDA-MB-231 cells were treated for 24 and 48 h. Methods: Intracellular proteins were extracted, digested with trypsin, and analyzed by label-free LC-2D-MS/MS using HDMSE acquisition. Differentially expressed proteins were identified and quantified using the Progenesis QI platform, and then functional classification and pathway enrichment analyses were performed. Results: A total of 2818 proteins were identified, of which 2150 displayed time-dependent modulation following treatment. After 24 h, cells exhibited an adaptive stress response profile characterized by increased DNA repair proteins (CHEK1, CDK12), migration/remodeling factors (LAMA4, CTTN, A2M), and immune/cell cycle regulators (PER2, HLA-B), while antioxidant proteins (SOD1, GPX1) and BRCA1 were reduced, indicating oxidative stress and DNA damage. After 48 h, the proteomic profile shifted toward cell death, with increased PARK7, OPA1, ATL3, and CASP8 expression, disruption of DNA repair and cell cycle regulators (CHEK1, CDK12, MSH6, KIF2C), and decreased migration-related proteins (LAMA4, CTTN, ITGB3, A2M). Conclusions: Nano-encapsulated tarin promotes a time-dependent transition from early adaptive stress responses to apoptosis, autophagy, cell cycle disruption, and loss of migratory capacity. These findings provide novel insights into the molecular mechanisms underlying tarin antitumoral activity and support its potential as a promising therapeutic strategy against triple-negative breast cancer. Full article
(This article belongs to the Special Issue Natural Compounds in Drug Delivery Systems)
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24 pages, 16114 KB  
Article
West Asian Art in the Murals of Zhang Shiqing’s Tomb: Cultural Selection and Visual Representation in the Context of Local Adaptation
by Xinyu Wang, Zhijun Wang and Rigen Mo
Arts 2026, 15(9), 207; https://doi.org/10.3390/arts15090207 - 7 Sep 2026
Abstract
The Liao Dynasty culture among the northern nomadic peoples absorbed profound West Asian historical heritage and uniquely ingenious artistic essence to enrich its own diversity. These mural paintings of Liao tombs most concentratedly reflect this phenomenon. As a visual medium for cultural integration [...] Read more.
The Liao Dynasty culture among the northern nomadic peoples absorbed profound West Asian historical heritage and uniquely ingenious artistic essence to enrich its own diversity. These mural paintings of Liao tombs most concentratedly reflect this phenomenon. As a visual medium for cultural integration along the Steppe Silk Roads, their artistic expression profoundly reflects the Liao Dynasty’s process of absorbing West Asian art. This article examines the tomb of Zhang Shiqing 张世卿, a former Song subject, now an official of the Liao Dynasty. It employs image analysis alongside interdisciplinary theories from art history, geography, archaeology, and history, aiming to reveal the logic of localized adaptation of West Asian artistic elements—the zodiac signs (Greek: zōidiakos kyklos, “circle of animals”; Chinese: 黄道十二宫图) and the curved-neck pipa—within the murals. The article argues that multiple underlying factors within the Liao Dynasty’s political-cultural structure, Buddhist propagation, and functional demands drove both the zodiac signs and the curved-neck pipa to exhibit a pattern of knowledge-integration adaptation. This adaptation manifests as juxtaposition and fusion in visual composition, functional integration and recontextualization in spatial arrangement, achieving a creative transformation of West Asian artistic motifs. This process not only revitalized the ritual space of the murals but also represented the inevitable projection of dualistic systems within the cultural sphere of the Liao Dynasty. Full article
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18 pages, 2493 KB  
Article
Efficient Enrichment of Ultra-Low-Grade Associated Tantalum–Niobium Ore via Sodium Silicate Pre-Dispersion Combined with Gravity Separation: Mechanism and Performance
by Lei Wang, Guocheng Yao, Xinyue Shi, He Shang, Hongxia Li and Meilin Liu
Minerals 2026, 16(9), 919; https://doi.org/10.3390/min16090919 (registering DOI) - 6 Sep 2026
Abstract
Tantalum and niobium are critical strategic rare refractory metals; however, most associated tantalum–niobium resources are characterized by ultra-low grade, finely disseminated grains, and severe argillization, which causes pronounced slime coating of gangue mica on valuable mineral surfaces and impedes efficient recovery via gravity [...] Read more.
Tantalum and niobium are critical strategic rare refractory metals; however, most associated tantalum–niobium resources are characterized by ultra-low grade, finely disseminated grains, and severe argillization, which causes pronounced slime coating of gangue mica on valuable mineral surfaces and impedes efficient recovery via gravity separation. In this study, an innovative beneficiation route combining sodium silicate pre-dispersion conditioning with shaking-table gravity separation was proposed to recover a spodumene-dominant pegmatitic lithium ore containing trace associated Nb–Ta minerals, with mica as the major slime-forming gangue. Process mineralogy analysis revealed that the raw ore has a total (Nb,Ta)2O5 grade of only 0.019%, with the main valuable minerals being columbite-(Mn), columbite–tantalite, and tantalite, whereas layered mica minerals constitute the primary argillization gangue that readily generates micro-fine slimes smaller than 5 μm. Single-factor tests demonstrated that the optimal grinding fineness was 84.4% passing 200 mesh, and the optimal feed pulp density for gravity separation was 28.6%. Adjusting pulp concentration alone, without a dispersant, yielded a Nb2O5 concentrate grade of merely 0.144%, as severe slime coating greatly limited separation selectivity. Following the introduction of sodium silicate for pre-dispersion, the separation performance improved markedly at the optimal dosage of 300 g/t: the concentrate Nb2O5 grade reached 1.28% (8-fold higher than the blank test), and the Ta2O5 grade increased to 0.47% (85-fold higher than the blank test). Multi-scale characterization, including zeta potential measurements, ultraviolet–visible (UV–vis) diffuse reflectance spectroscopy, Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), was employed to elucidate the dispersion mechanism of sodium silicate. The results confirmed that sodium silicate undergoes selective chemisorption on mica surfaces by forming Si–O–Al bonds with surface Al–OH active sites, which substantially increases electrostatic repulsion between mineral particles and eliminates mica slime coating on tantalum–niobium minerals. In contrast, sodium silicate exhibits only weak physical adsorption on tantalum–niobium mineral surfaces, with no evident chemical bonding. This work provides a low-cost, eco-friendly pretreatment–gravity separation coupling technology for the efficient enrichment of argillized ultra-low-grade tantalum–niobium associated ores and offers theoretical guidance for the green utilization of complex tantalum–niobium tailings and low-grade mineral resources. Full article
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15 pages, 2406 KB  
Article
scFlowReport: A Reproducible Workflow for Comparative Downstream Biological Analysis of Single-Cell RNA-seq Data
by Nayoung Park, Hyewon Lee and Jaebum Kim
Biomolecules 2026, 16(9), 1288; https://doi.org/10.3390/biom16091288 - 6 Sep 2026
Abstract
Single-cell RNA sequencing (scRNA-seq) studies are frequently organized around comparisons—disease versus control, treatment response, or genetic perturbation—yet biological interpretation still depends on integrating multiple independent downstream analyses for differential expression, functional enrichment, regulatory network inference, and cell–cell communication analysis. Applying these tools consistently [...] Read more.
Single-cell RNA sequencing (scRNA-seq) studies are frequently organized around comparisons—disease versus control, treatment response, or genetic perturbation—yet biological interpretation still depends on integrating multiple independent downstream analyses for differential expression, functional enrichment, regulatory network inference, and cell–cell communication analysis. Applying these tools consistently across comparisons typically requires substantial custom scripting, and their heterogeneous outputs must be manually harmonized before the results can be compared or reported together. We present scFlowReport, a lightweight, configuration-driven workflow that propagates a single user-defined comparison across cell-level and sample-aware pseudobulk differential expression, over-representation and ranked functional enrichment, transcription-factor regulon export for SCENIC, and group-resolved LIANA cell–cell communication analysis, starting from an already annotated Seurat object. The workflow automatically compiles complementary downstream results into standardized figures, summary tables, and a self-contained static HTML report that can be readily inspected and shared without requiring a persistent server. Application of scFlowReport to a publicly available Atopic Dermatitis scRNA-seq dataset demonstrated its utility by enabling researchers to obtain complementary biological evidence from multiple established downstream analyses. By coordinating complementary downstream analyses under a shared comparison framework, scFlowReport provides a practical and reproducible workflow for systematic interpretation of comparative single-cell transcriptomic data. Full article
(This article belongs to the Section Bioinformatics and Systems Biology)
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20 pages, 5670 KB  
Review
Biomolecular Condensates Integrate Transcriptional and Epigenetic Responses to Hypoxia
by Chinmaya Kumar Patel, Ahmed Saif and Xiaojun Ren
Int. J. Mol. Sci. 2026, 27(17), 7926; https://doi.org/10.3390/ijms27177926 (registering DOI) - 5 Sep 2026
Abstract
Hypoxia is a defining feature of physiological stress and the core of solid tumors, where aberrant vascularization limits oxygen delivery; cells respond through mechanisms that extend beyond the canonical stabilization of hypoxia-inducible factors (HIFs). Recent studies suggest that hypoxia can promote the formation [...] Read more.
Hypoxia is a defining feature of physiological stress and the core of solid tumors, where aberrant vascularization limits oxygen delivery; cells respond through mechanisms that extend beyond the canonical stabilization of hypoxia-inducible factors (HIFs). Recent studies suggest that hypoxia can promote the formation of specific biomolecular conden-sates, membraneless compartments generated through liquid–liquid phase separation in which regulatory proteins and RNAs become locally enriched at genomic regions, while chromatin mainly serves as an organizational scaffold. Transcription factors, the coacti-vators p300/CBP, Mediator, and BRD4, chromatin-modifying enzymes, and architectural RNAs such as NEAT1 and MALAT1 partition into these compartments, and their con-densation can help reorganize local chromatin structure and enhancer–promoter interac-tions. Because molecular oxygen is a shared co-substrate for the Jumonji-C histone demethylases and the ten-eleven translocation (TET) DNA dioxygenases, hypoxia reshapes histone methylation and DNA methylation in parallel, and readers that bridge these marks, including UHRF1, may participate in condensate-associated chromatin regulation. Hypoxia-driven condensation of ZHX2 rewires enhancer–promoter contacts and higher-order genome architecture, influencing cell identity, stemness, and metastatic potential, and Polycomb condensates represent another candidate epigenetic compartment that may be influenced by hypoxic signaling. These processes may be particularly important in cancer, where chronic hypoxia provides a sustained stimulus for condensate formation and epigenetic remodeling. Together, these findings support a model in which phase separation and epigenetic reprogramming are not separate layers but one integrated response to low oxygen, offering opportunities to target maladaptive condensates in disease. Full article
(This article belongs to the Special Issue Molecular Regulatory Mechanisms in the Hypoxic Environment)
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23 pages, 4259 KB  
Article
A Comparative Genomic Assessment of Invasive Potential in the Planthopper Orosanga japonica (Hemiptera: Ricaniidae)
by Yusuf Ulaş Çınar, Mehmet Ali Balcı, Onur Obut, Tuana Öğretici, Selahattin Barış Çay, Hüsna Yağmur Dural, Fatih Dikmen, Yakup Bakır and Vahap Eldem
Insects 2026, 17(9), 932; https://doi.org/10.3390/insects17090932 (registering DOI) - 5 Sep 2026
Abstract
Orosanga japonica (Hemiptera: Ricaniidae) is an invasive, polyphagous planthopper established in Türkiye since 2007 that threatens economically important perennial and field crops across the Black Sea region. Although its establishment and rapid spread suggest considerable adaptive capacity, the genomic basis of this potential [...] Read more.
Orosanga japonica (Hemiptera: Ricaniidae) is an invasive, polyphagous planthopper established in Türkiye since 2007 that threatens economically important perennial and field crops across the Black Sea region. Although its establishment and rapid spread suggest considerable adaptive capacity, the genomic basis of this potential remains unexplored. We combined whole-genome sequencing with RNA-Seq data to generate a functionally annotated genome, recovering 92.5% of conserved single-copy orthologs. Utilizing these resources, we performed comparative genomic analyses across 20 additional hemipteran and thysanopteran species, investigating gene family dynamics and genome-wide positive selection. These analyses revealed 52 gene families with statistically significant, lineage-specific size changes (24 expansions and 28 contractions): expanded families were enriched for C2H2 zinc-finger transcription factors, α/β-hydrolases, major facilitator transporters, serpins, and chemosensory proteins, whereas contracted families included a cytochrome P450 family. Additionally, branch site tests identified 122 candidate genes under lineage-specific positive selection. These loci fall into three functional categories potentially associated with invasion-related traits: host detection and neuronal excitability, stress tolerance (xenobiotic, oxidative, and proteostatic), and barrier remodeling. Together, these genomic signatures highlight candidate molecular mechanisms that may contribute to host detection, xenobiotic tolerance, and ecological plasticity, providing a framework for evolutionary analysis and the targeted management of this emerging agricultural pest. Full article
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26 pages, 1966 KB  
Article
Thiol-Functionalized Magnetic Biochar-Mediated Matrix Cleanup and Selective Enrichment for Trace-Level Rapid Determination of Cadmium in Environmental Water and Aquatic Products
by Lei Zhu, Xizhuang Zhu, Zhuping Liu, Longxiang Fang, Liping Qiu, Shunlong Meng and Chao Song
Toxics 2026, 14(9), 785; https://doi.org/10.3390/toxics14090785 (registering DOI) - 5 Sep 2026
Abstract
Efficient enrichment and rapid determination of trace cadmium (Cd2+) in complex environmental and food matrices remain challenging because of severe matrix interference and insufficient sample pretreatment efficiency. Herein, a thiol-functionalized silica-coated magnetic biochar (MBC@SiO2–SH) was developed as a selective [...] Read more.
Efficient enrichment and rapid determination of trace cadmium (Cd2+) in complex environmental and food matrices remain challenging because of severe matrix interference and insufficient sample pretreatment efficiency. Herein, a thiol-functionalized silica-coated magnetic biochar (MBC@SiO2–SH) was developed as a selective magnetic adsorbent and integrated with a homogeneous chemiluminescence immunoassay (CLIA) to establish an enrichment-assisted analytical strategy for trace Cd2+ determination in environmental water and aquatic products. Owing to its abundant thiol coordination sites, large specific surface area, and excellent magnetic responsiveness, MBC@SiO2–SH exhibited a high practical Cd2+ enrichment capacity (82.65 mg/g) under high-loading conditions, remarkable selectivity, and good reusability toward Cd2+. Adsorption kinetic, isotherm, thermodynamic, and X-ray photoelectron spectroscopy analyses revealed that Cd2+ uptake was predominantly governed by Cd–S coordination accompanied by physical adsorption. Under the optimized fixed-bed enrichment conditions, the proposed column achieved a preconcentration factor of approximately 40, enabling efficient matrix cleanup and selective enrichment prior to CLIA. The integrated method exhibited excellent analytical performance for both environmental water and aquatic products, with recoveries of 92.26–118.64% and 92.41–108%, respectively, and showed good agreement with ICP-MS. By coupling selective magnetic preconcentration with rapid homogeneous immunodetection, the proposed strategy provides a simple, sensitive, and efficient analytical platform for routine monitoring of trace Cd2+ and offers a generalizable framework for enrichment-assisted rapid analysis of trace contaminants in complex environmental and food matrices. Full article
18 pages, 15910 KB  
Article
Identification and Expression Analysis of SHN Gene Family in Melon
by Zhu Lian, Mengze Li, Xiaoyu Wang, Meng Li, Lan Li, Xuxu Niu, Xiang Li, Juan Hou, Qiong Li, Wenwen Mao, Lili Li, Chen Luo, Jianbin Hu and Panqiao Wang
Horticulturae 2026, 12(9), 1125; https://doi.org/10.3390/horticulturae12091125 - 5 Sep 2026
Abstract
SHN (SHINE) transcription factors belong to the AP2/ERF superfamily. They regulate cuticular wax biosynthesis and abiotic stress responses in plants, and play crucial roles in fruit netting development of cucurbit crops. However, a systematic genome-wide analysis of the SHN gene family in melon [...] Read more.
SHN (SHINE) transcription factors belong to the AP2/ERF superfamily. They regulate cuticular wax biosynthesis and abiotic stress responses in plants, and play crucial roles in fruit netting development of cucurbit crops. However, a systematic genome-wide analysis of the SHN gene family in melon has not yet been reported. In this study, the thick-skinned melon cultivar ‘L5283’ was used as experimental material, and nine CmSHN family members were identified at the whole-genome level. We systematically analyzed their physicochemical properties, chromosomal distribution, evolutionary conservation, promoter cis-acting elements, and expression patterns under four types of stresses. The results showed that the nine CmSHN genes were unevenly distributed across six chromosomes. Extensive synteny was observed among SHN genes of cucurbit species including melon, watermelon and cucumber, with higher genomic structural conservation detected between cucumber and melon. Six categories of cis-elements were enriched in CmSHN gene promoters, namely light-responsive, hormone-responsive, stress-related, and development-associated elements, along with circadian rhythm and flavonoid biosynthesis elements. Light-responsive elements were the most abundant, suggesting that light signals may contribute to the regulation of CmSHN transcription. RT-qPCR analysis under ABA, cold, drought and salt stresses revealed that all CmSHN genes were induced to varying degrees, with obvious differences in response patterns and duration. Notably, CmSHN7 exhibited markedly higher fold induction than other family members under all four stress treatments. This study systematically characterizes the fundamental features and stress response patterns of the CmSHN family in melon, provides baseline data for elucidating the molecular mechanisms underlying wax biosynthesis and fruit netting formation, and supplies candidate genes for molecular breeding of stress resistance in cucurbit crops. Full article
(This article belongs to the Special Issue Cucurbitaceae Genetics, Physiology and Breeding)
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20 pages, 423 KB  
Article
Diverging Paths: Heterogeneity in Early Childhood Executive Function Development in Chile
by Camila Martínez, Pamela Soto-Ramírez and Marigen Narea
Brain Sci. 2026, 16(9), 946; https://doi.org/10.3390/brainsci16090946 (registering DOI) - 5 Sep 2026
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Abstract
Background/Objectives: Executive function (EF) is a foundational cognitive process associated with academic achievement and socioemotional adjustment. While average developmental trends are well documented, less is known about heterogeneity in EF trajectories during early childhood and the contextual factors associated with different developmental pathways. [...] Read more.
Background/Objectives: Executive function (EF) is a foundational cognitive process associated with academic achievement and socioemotional adjustment. While average developmental trends are well documented, less is known about heterogeneity in EF trajectories during early childhood and the contextual factors associated with different developmental pathways. This study examined longitudinal trajectories of EF between ages 3 and 6 and their associations with family, child, and caregiver well-being, as well as the home environment. Methods: Data were drawn from the Chilean longitudinal cohort First Thousand Days (Mil Primeros Días [MPD]; n = 583). EF was assessed at ages 3, 5, and 6 using the Cat-Dog task. Latent profile analysis identified EF trajectories, and multinomial logistic regression examined predictors of trajectory membership. Results: Three EF trajectories were identified: Normative (54.5%), Persistently Disadvantaged (34.6%), and Advantaged Accelerating (10.8%). Home environment quality was the most consistent predictor of trajectory membership, increasing the likelihood of following the Advantaged Accelerating (RRR = 1.59) or Normative (RRR = 1.21) trajectory relative to the Persistently Disadvantaged trajectory. Early cognitive development protected against the most disadvantaged trajectory, whereas distal sociodemographic characteristics and caregiver well-being were not significant predictors of trajectory membership. Conclusions: Individual differences in EF emerge early and show divergent growth rates through age 6, with home environment quality as the strongest predictor—highlighting the value of enriching home learning environments before school entry. Full article
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31 pages, 21058 KB  
Article
Structural Characterization and In Vivo Gastric Mucosal Protective Activity of a Polysaccharide from Laoxianghuang (Fermented Finger Citron) in Mice
by Heming Liu, Cheng Zhong, Dan Yang, Yuxiao Wu, Junyun Luo and Aimei Zhou
Int. J. Mol. Sci. 2026, 27(17), 7919; https://doi.org/10.3390/ijms27177919 (registering DOI) - 5 Sep 2026
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Abstract
PFCP-2-1 (polysaccharide-2-1 of Finger Citron-pickled products), a water-soluble polysaccharide enriched in galacturonic acid, was isolated from Laoxianghuang by hot water extraction and purified using DEAE-52 and agarose CL-6B chromatography. Structural analysis showed that PFCP-2-1 had a smooth surface, flakes of varying sizes and [...] Read more.
PFCP-2-1 (polysaccharide-2-1 of Finger Citron-pickled products), a water-soluble polysaccharide enriched in galacturonic acid, was isolated from Laoxianghuang by hot water extraction and purified using DEAE-52 and agarose CL-6B chromatography. Structural analysis showed that PFCP-2-1 had a smooth surface, flakes of varying sizes and shapes, irregular ellipsoidal structures, and cylindrical-like forms, which likely represent aggregated assemblies formed by the association and curling of polysaccharide chains. It was determined to have an average molecular weight of 749.38 kDa and to consist of rhamnose, galactose, glucose, and galacturonic acid (molar ratio 0.147:0.238:0.059:0.556). FT-IR spectroscopy revealed both α- and β-pyranose configurations, while methylation and NMR analyses identified 16 types of glycosidic linkages, of which 9 were the main types, consistent with a pectic-type structure. In an ethanol-induced acute gastric ulcer mouse model, PFCP-2-1 exhibited significant mucosal protection by elevating prostaglandin E2 (PGE2), transforming growth factor-α (TGF-α), and mucin 5AC (MUC5AC) levels and upregulating Occludin and zonula occludens-1 (ZO-1) expression. It also modulated the gut microbiota by increasing the abundance of Bacteroides and Prevotella_UCG-001, and enhanced short-chain fatty acid (acetate and butyrate) levels. These findings suggest that PFCP-2-1 may exhibit a protective effect against ethanol-induced gastric damage under the conditions of this experiment, suggesting its potential for further development as a functional food ingredient. Full article
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20 pages, 2740 KB  
Article
Phenotype-Specific Pharmacogenetic Patterns of Methotrexate Neurotoxicity in Pediatric Acute Lymphoblastic Leukemia
by Javier Gómez-Román, Juan C. Restrepo, Luz M. González, Laura González-Rodríguez, Ángela Lacombe-Antoneli, Yolanda Gutiérrez-Martín, María Dolores de la Maya, Montserrat Mesegué, José Luis Dapena, Ana Carbone, Berta González Martínez, Francisco Lendínez Molinos, Antonio Molinés Honrubia, Miriam Abós García, Marina García Morín, Samuel Navarro Noguera, María Sagaseta de Ilurdoz, Itziar Astigarraga, Maria Baro Fernández, Jaime Verdú Amorós, Alexandra Regueiro, Manuel Ramírez Orellana, José Luis Fuster Soler, Soledad González Muñiz, Adela Cañete Nieto, Montserrat Torrent Español, Héctor González Méndez, Jose M. Vagace and Guillermo Gervasiniadd Show full author list remove Hide full author list
J. Clin. Med. 2026, 15(17), 6877; https://doi.org/10.3390/jcm15176877 (registering DOI) - 5 Sep 2026
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Abstract
Background: Methotrexate-induced neurotoxicity (MTX-NTX) is a severe complication during childhood acute lymphoblastic leukemia (ALL) treatment, yet its underlying pharmacogenetic determinants remain incompletely understood. Methods: A multicenter retrospective nationwide case–control study was performed including 71 pediatric ALL patients (34 MTX-NTX cases and 37 controls). [...] Read more.
Background: Methotrexate-induced neurotoxicity (MTX-NTX) is a severe complication during childhood acute lymphoblastic leukemia (ALL) treatment, yet its underlying pharmacogenetic determinants remain incompletely understood. Methods: A multicenter retrospective nationwide case–control study was performed including 71 pediatric ALL patients (34 MTX-NTX cases and 37 controls). Targeted next-generation sequencing of 17 genes involved in MTX transport, intracellular metabolism and folate pathways was performed. Results: Transport-related genes accounted for 61.4% of all detected variants and showed the highest number of nominally significant variants. Pathway-level burden analysis demonstrated a significant enrichment of transporter-related variants in patients with MTX-NTX compared with controls (FDR-adjusted p = 0.004), whereas the analysis for folate/metabolism-related genes did not remain significant after multiple-testing (FDR-adjusted p = 0.096). Similar findings were observed in the stroke-like syndrome (SLS) subgroup (FDR-adjusted p = 0.014 and 0.108, respectively). Gene-level burden analysis identified ABCG2 and ABCC4 as the predominant contributors, harboring both 18.4% of significant variants in the overall MTX-NTX analysis and 20.6% and 17.6%, respectively in the SLS phenotype. Moreover, the distribution of significant variants was strongly correlated between the overall MTX-NTX and SLS analyses (Spearman’s ρ = 0.549, p = 0.022). Volcano plot analysis revealed ABCG2 as the gene showing the most prominent pattern of nominal associations, containing both the variants associated with a protective direction (e.g., c.1728-46G>A, p = 2.6 × 10−4) and variants associated with increased risk, including c.34G>A and c.203+36A>G (p = 0.002) and c.263+10A>G (p = 0.0097). Phenotype-specific analyses revealed distinct genetic signatures across neurological manifestations, with transporter genes predominating in focal neurological deficits. Conclusions: Our findings suggest that genetic variability in ABC transporter genes may contribute to susceptibility to MTX-NTX, whereas folate metabolism genes may represent complementary phenotype-modifying factors. These findings are exploratory and require validation in larger, independent cohorts and functional studies. Full article
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17 pages, 4122 KB  
Article
Neonatal 2′-Fucosyllactose Supplementation Modulates Exploratory Behavior and Hippocampal Synaptic Plasticity in Rats Through Gut Microbiota and Metabolic Remodeling
by Miao Yu, Jin Wang, Ruixin Kou, Bingye Xu, Weiqian Zhang, Ying Zhang, Jingmin Liu and Shuo Wang
Foods 2026, 15(17), 3151; https://doi.org/10.3390/foods15173151 - 5 Sep 2026
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Abstract
2′-Fucosyllactose (2′-FL) represents a significant constituent within human milk oligosaccharides, and its benefits for intestinal health and neurodevelopment in infants and young children have been widely recognized. However, the mechanism by which 2′-FL influences early-life behavioral development through the gut–brain axis remains incompletely [...] Read more.
2′-Fucosyllactose (2′-FL) represents a significant constituent within human milk oligosaccharides, and its benefits for intestinal health and neurodevelopment in infants and young children have been widely recognized. However, the mechanism by which 2′-FL influences early-life behavioral development through the gut–brain axis remains incompletely understood. In this study, we investigated the effects of neonatal 2′-FL supplementation on behavioral development in Sprague-Dawley (SD) rats and explored its potential microbiota-metabolite regulatory mechanisms. After 4 consecutive weeks of oral gavage beginning on postnatal day 2, rats receiving 2′-FL showed significantly increased average movement speed and central-area exploration time in the open field test. From a systemic perspective, 2′-FL lowered blood diamine oxidase (DAO) and D-lactic acid (D-LA) concentrations while elevating colonic mRNA levels of tight junction protein-related genes, consequently enhancing intestinal barrier stability. In addition, 16S rRNA sequencing showed that 2′-FL reshaped the gut microbiota structure and significantly enriched Lactobacillus, Bacteroides, and short-chain fatty acid (SCFA)-associated taxa represented by Lachnospiraceae_NK4A136_group. Untargeted metabolomics revealed that 2′-FL induced systemic metabolic remodeling, characterized by upregulation of the bioactive metabolites dehydroepiandrosterone sulfate (DHEA-S) and deoxycholic acid (DCA), and downregulation of the glucocorticoid-related corticosterone. Western blot validation further showed higher hippocampal protein expression of postsynaptic density protein 95 (PSD95), brain-derived neurotrophic factor (BDNF), and synaptophysin in the 2′-FL group, supporting enhanced synaptic plasticity-related signaling. In summary, neonatal 2′-FL intervention enhanced exploratory behavior and was accompanied by increased hippocampal synaptic plasticity-related protein expression in rats, potentially through coordinated regulation of gut microbiota composition and systemic metabolism. Full article
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25 pages, 9341 KB  
Article
Systematic Analysis of MRTFB Phosphoproteomic Datasets Reveals Co-Regulated Kinase Networks and Co-Occurring Phosphosites Associated with the Actin Cytoskeleton Pathway
by Jetna John, Vaishnavi Gopalakrishnan, Suhail Subair, Athira Perunelly Gopalakrishnan, Akhina Palollathil and Rajesh Raju
Curr. Issues Mol. Biol. 2026, 48(9), 910; https://doi.org/10.3390/cimb48090910 (registering DOI) - 5 Sep 2026
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Abstract
Background: Myocardin-related transcription factor B (MRTFB) acts as a transcriptional coactivator for serum response factor (SRF) and regulates actin cytoskeletal dynamics. Despite its biological significance, the phosphoregulatory network, upstream kinases, and interactors remain poorly understood. Methods: To explore this, we analyzed global phosphoproteomic [...] Read more.
Background: Myocardin-related transcription factor B (MRTFB) acts as a transcriptional coactivator for serum response factor (SRF) and regulates actin cytoskeletal dynamics. Despite its biological significance, the phosphoregulatory network, upstream kinases, and interactors remain poorly understood. Methods: To explore this, we analyzed global phosphoproteomic datasets to identify predominant phosphosites. We categorized phosphosites in other proteins as positively or negatively co-regulated with the predominant phosphosites of MRTFB and also integrated predicted upstream kinases and interactors of MRTFB. Further, phosphosite conservation, co-occurrence patterns, and functional and pathway enrichment analyses of co-regulated proteins were also performed. Results: We identified S66 and S921 as predominant phosphosites in MRTFB, with the highest detection frequency across multiple experimental conditions. These phosphosites were found to be conserved within the MRTF family and across multiple species. From the predicted upstream kinases, MAPK1, MAPK3, MAST3, and CSNK1A1 were identified as predicted upstream kinases. Co-occurrence analysis revealed high positive co-occurrence between the predominant phosphosites, S66 and S921, suggesting similar functional roles. Functional enrichment analysis highlighted the involvement of co-regulated proteins in the actin cytoskeleton pathway. Conclusions: This study provides the detailed phosphoproteomic landscape of MRTFB, mapping its upstream kinases and co-regulated proteins involved in actin cytoskeleton regulation. Full article
(This article belongs to the Section Bioinformatics and Systems Biology)
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15 pages, 8220 KB  
Article
Transcriptomic and Biochemical Responses of Camellia sinensis (L.) Kuntze Callus Cultures to Nitrogen Deficiency In Vitro
by Karina A. Manakhova, Maya V. Gvasaliya, Lyudmila S. Malyukova, Lada V. Zhokhova, Alexey V. Ryndin and Evgeny I. Rogaev
Nitrogen 2026, 7(3), 98; https://doi.org/10.3390/nitrogen7030098 - 4 Sep 2026
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Abstract
Nitrogen deficiency is one of the key factors limiting the growth and raw-material quality of tea plants; however, cell-autonomous mechanisms underlying the response of Camellia sinensis (L.) Kuntze to reduced nitrogen availability remain insufficiently studied. This study characterized biochemical and transcriptomic changes in [...] Read more.
Nitrogen deficiency is one of the key factors limiting the growth and raw-material quality of tea plants; however, cell-autonomous mechanisms underlying the response of Camellia sinensis (L.) Kuntze to reduced nitrogen availability remain insufficiently studied. This study characterized biochemical and transcriptomic changes in callus cultures of three tea cultivars (‘Kolkhida’, ‘Karatum’, and cultivar #582) after two months of cultivation on Murashige–Skoog medium lacking nitrogen-containing components. Nitrogen withdrawal caused visible stress symptoms, reduced total nitrogen in ‘Kolkhida’ and ‘Karatum’ (total nitrogen was not determined in cultivar #582), and altered the accumulation of L-theanine, caffeine, and catechins in a cultivar-dependent manner. ‘Kolkhida’ showed decreases in simple catechins, L-theanine, and caffeine; ‘Karatum’ showed increases in simple and gallated catechins together with a decrease in L-theanine; and cultivar #582 showed smaller changes in most measured biochemical traits. RNA-seq identified 1898 differentially expressed genes (DEGs) in ‘Kolkhida’, 4551 in ‘Karatum’, and 9869 in cultivar #582. The enriched Gene Ontology term “response to karrikin” (GO:0080167) was common to all three cultivars, whereas cultivar-specific profiles differed substantially. In the flavonoid biosynthesis pathway, key phenylpropanoid genes were predominantly downregulated in cultivar #582 but induced in ‘Kolkhida’ and ‘Karatum’. RT-qPCR confirmed the direction of change for selected genes. Under the tested in vitro conditions, ‘Kolkhida’ showed the strongest biochemical deterioration, whereas cultivar #582 combined the greatest biochemical stability with the most extensive transcriptomic remodeling. Because total nitrogen was not measured in cultivar #582, its apparent tolerance remains provisional. Tea callus cultures therefore provide a controlled discovery system for cell-autonomous candidate responses, but cultivar rankings and candidate markers require validation in independent callus lines and whole plants. Full article
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