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16 pages, 2687 KiB  
Article
Cloning and Functional Validation of the Candidate Gene LuWRKY39 Conferring Resistance to Septoria linicola (Speg.) Garassini from Flax
by Si Chen, Hongmei Yuan, Guangwen Wu, Xue Yang, Dandan Liu, Le Chen, Jing Chen, Yan Liu, Weiping Yin, Cen Li, Linlin Wu, Jun Ma, Daolin Bian and Liguo Zhang
Agriculture 2025, 15(14), 1561; https://doi.org/10.3390/agriculture15141561 - 21 Jul 2025
Viewed by 162
Abstract
WRKY transcription factors play key roles in plant immune responses, including resistance to fungal pathogens. In the present study, we identified a flax resistance-related gene Lus10021999, named LuWRKY39. Here, to identify the role of WRKY transcription factor in resistance of flax against [...] Read more.
WRKY transcription factors play key roles in plant immune responses, including resistance to fungal pathogens. In the present study, we identified a flax resistance-related gene Lus10021999, named LuWRKY39. Here, to identify the role of WRKY transcription factor in resistance of flax against Septoria linicola, we cloned and analyzed the gene LuWRKY39 via homologous cloning using bioinformatics methods and localized the encoded protein. Quantitative real-time PCR (qRT-PCR) was used to explore the response of this gene to S. linicola. The results showed that the gene that is 948 bp long exhibited the closest genetic relationship to WRKY in castor (Ricinus communis), as revealed by phylogenetic analysis, and the encoded protein was localized in the nucleus. The LuWRKY39 gene showed higher expression levels in resistant flax materials than in susceptible ones, and higher in roots and stems than in leaves. Furthermore, gene expression showed an upward trend following treatment with salicylic acid (SA) and methyl jasmonate (MeJA), indicating that LuWRKY39 is involved in the regulation of SA and JA signals. By silencing LuWRKY39 in flax using virus-induced gene silencing (VIGS), the processed plants were more sensitive to S. linicola than untreated plants. Gene expression analysis and disease index statistics confirmed that the silenced plants were more susceptible, highlighting the crucial role of LuWRKY39 in flax disease resistance. This study provides a foundation for functional investigations of WRKY genes in flax and the identification of disease resistance genes. Full article
(This article belongs to the Section Crop Genetics, Genomics and Breeding)
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25 pages, 657 KiB  
Article
Deficit Irrigation and Nitrogen Application Rate Influence Growth and Yield of Four Potato Cultivars (Solanum tuberosum L.)
by Abdulssamad M. H. Barka, Samuel Y. C. Essah and Jessica G. Davis
Horticulturae 2025, 11(7), 849; https://doi.org/10.3390/horticulturae11070849 - 18 Jul 2025
Viewed by 175
Abstract
Potatoes have high nitrogen (N) and irrigation requirements. Increasing water scarcity and environmental concerns highlight the need for efficient resource management. This study evaluated the effects of deficit irrigation and reduced N on yield and growth parameters in four potato cultivars (Canela Russet, [...] Read more.
Potatoes have high nitrogen (N) and irrigation requirements. Increasing water scarcity and environmental concerns highlight the need for efficient resource management. This study evaluated the effects of deficit irrigation and reduced N on yield and growth parameters in four potato cultivars (Canela Russet, Mesa Russet, Russet Norkotah3, and Yukon Gold) at Colorado State University’s San Luis Valley Research Center over two growing seasons. Three irrigation levels (~70%, ~80%, and 100% ET replacement) and two N rates (165 and 131 kg/ha) were evaluated. Measurements included total and marketable yield, tuber size distribution, tuber bulking (TB), leaf area index (LAI), and stem and tuber numbers. Yield losses were absent with ≤18% irrigation reduction in Canela Russet, Mesa Russet, or Yukon Gold but occurred with larger deficits. Russet Norkotah3 experienced yield decline with 16–23% reductions in irrigation. A twenty percent reduction in N application had no effect on Mesa Russet or Russet Norkotah3 yields, while the other varieties experienced a yield decline in one out of two years. Early-season LAI and late-season TB were positively correlated with yield, particularly for Canela Russet and Russet Norkotah3. These findings suggest irrigation and N inputs can be reduced without compromising productivity, but reductions must be determined on a cultivar-by-cultivar basis. Full article
(This article belongs to the Special Issue Advances in Sustainable Cultivation of Horticultural Crops)
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20 pages, 2609 KiB  
Article
Priming ‘Santa Isabel’ Pea (Pisum sativum L.) Seeds with NaCl and H2O2 as a Strategy to Promote Germination
by Javier Giovanni Álvarez-Herrera, Julián Stiven Lozano and Oscar Humberto Alvarado-Sanabria
Seeds 2025, 4(3), 34; https://doi.org/10.3390/seeds4030034 - 17 Jul 2025
Viewed by 143
Abstract
Peas possess significant nutritional properties due to their high protein levels, carbohydrates, fiber, and vitamins. Increased climate variability can lead to water stress in crops like peas. Therefore, priming plants through seed priming is a technique that has proven effective as a pre-conditioning [...] Read more.
Peas possess significant nutritional properties due to their high protein levels, carbohydrates, fiber, and vitamins. Increased climate variability can lead to water stress in crops like peas. Therefore, priming plants through seed priming is a technique that has proven effective as a pre-conditioning method for plants to cope with more severe future stresses. Different doses and soaking times of ‘Santa Isabel’ pea seeds in NaCl and H2O2 were evaluated to enhance and promote germination. Two experiments were conducted under controlled conditions (average temperature 15.8 °C) through a completely randomized design with a 4 × 3 factorial arrangement, comprising 12 treatments in each trial. In the first trial, NaCl doses (0, 50, 100, or 150 mM) and the soaking time of the seeds in NaCl (12, 24, or 36 h) were examined. In the second trial, H2O2 doses (0, 20, 40, or 60 mM) were tested with the same imbibition times. The 50 mM NaCl dose at 24 h demonstrated the best values for germination rate index, mean germination time, germination rate (GR), and germination potential (GP). Seed imbibition for 24 h in NaCl, as well as in H2O2, is the ideal time to achieve the best GR and GP. The dry mass of leaf and stipule recorded the highest values with a 60 mM dose of H2O2 and 24 h of imbibition. An application of 150 mM NaCl resulted in the highest values of germinated seed dry mass, while causing lower dry mass in roots, stems, leaves, and stipules; however, it maintained similar total dry mass values. Full article
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21 pages, 474 KiB  
Review
Sustainable STEM Education in Arab Countries: Features and Challenges
by Rania Bou Saad, Ariadna Llorens Garcia and Jose M. Cabre Garcia
Sustainability 2025, 17(14), 6503; https://doi.org/10.3390/su17146503 - 16 Jul 2025
Viewed by 288
Abstract
This paper investigates how sustainable STEM education is being shaped within the pre-university systems of the 22 Arab countries. By categorizing these systems into four groups based on the Global Knowledge Index and two analytical tracks, this study examines in detail the factors [...] Read more.
This paper investigates how sustainable STEM education is being shaped within the pre-university systems of the 22 Arab countries. By categorizing these systems into four groups based on the Global Knowledge Index and two analytical tracks, this study examines in detail the factors that enable—or hinder—the development of long-term, sustainability-oriented competencies in science, technology, engineering, and mathematics. Beyond pedagogical dimensions, this study emphasizes STEM education as a strategic tool for achieving national sustainable development goals (SDGs), promoting workforce readiness, and informing education policy reform. The analysis highlights the policy efforts, systemic limitations, and the need for localized strategies to integrate sustainability into the STEM curricula and teacher training. It is structured in six sections: (1) an introduction to STEM and sustainability concepts, the Global Knowledge Index, and the Arab-region education landscape; (2) research questions, methodology, and data sources; (3) analysis of Groups 1 and 2, assessing their experiences in implementing sustainability-driven STEM initiatives; (4) analysis of Groups 3 and 4, evaluating their readiness for adopting sustainable STEM programs; (5) discussion of findings in light of sustainability policy frameworks; and (6) a concluding overview with actionable recommendations to align national education systems with global sustainability goals. Full article
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20 pages, 3828 KiB  
Article
Phylogenetic Structure Shifts Across Life-History Stages in Response to Microtopography and Competition in Subtropical Forests
by Weiqi Meng, Haonan Zhang, Lianhao Sun, Jianing Xu, Yajun Qiao and Haidong Li
Plants 2025, 14(14), 2098; https://doi.org/10.3390/plants14142098 - 8 Jul 2025
Viewed by 301
Abstract
This study focuses on a subtropical evergreen broad-leaved forest in China, utilizing a large permanent plot established in the Yaoluoping National Nature Reserve. By integrating data from a full-stem census and total station surveying, we analyzed the phylogenetic structure of the plant community [...] Read more.
This study focuses on a subtropical evergreen broad-leaved forest in China, utilizing a large permanent plot established in the Yaoluoping National Nature Reserve. By integrating data from a full-stem census and total station surveying, we analyzed the phylogenetic structure of the plant community as a whole and across different life-history stages (saplings, juveniles, and adults) while quantitatively assessing microtopographic variables and an interspecific competition index. The results indicate that the overall community in the Yaoluoping plot exhibited a weakly overdispersed pattern, and key microtopographic factors—including aspect, terrain position index (TPI), terrain ruggedness index (TRI), roughness, and flow direction—significantly influenced the evolution of phylogenetic structure. Distinctions were also observed among saplings, juveniles, and adults in phylogenetic structuring across life-history stages. Specifically, saplings displayed a higher degree of phylogenetic clustering, significantly influenced by density, elevation, TPI, and flow direction—suggesting that environmental filtering predominates at this stage, possibly due to lower environmental tolerance, limited dispersal ability, and conspecific negative density dependence. In contrast, juveniles and adults showed a more dispersed phylogenetic structure, with density, interspecific competition, aspect, TRI, TPI, and roughness significantly correlated with phylogenetic patterns, indicating that competition and niche differentiation become increasingly important as trees mature and establish within the community. Interspecific competition was found to play a crucial role in community structuring: the competition index was generally negatively correlated with the net relatedness index (NRI) and nearest taxon index (NTI) in juveniles and adults, implying that intense competition leads to the exclusion of some species and reduces overall diversity, with the strength and significance of competitive effects differing across stages. This study enhances our understanding of the complex interplay between microtopography and interspecific competition in shaping the phylogenetic structure and diversity of subtropical evergreen broad-leaved forests, elucidates the coupled mechanisms among microtopography, phylogenetic structure, and competition, and provides a scientific basis for forest conservation and management. Full article
(This article belongs to the Special Issue Origin and Evolution of the East Asian Flora (EAF)—2nd Edition)
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38 pages, 855 KiB  
Review
Failure Mode and Effects Analysis Integrated with Multi-Attribute Decision-Making Methods Under Uncertainty: A Systematic Literature Review
by Aleksandar Aleksić, Danijela Tadić, Nikola Komatina and Snežana Nestić
Mathematics 2025, 13(13), 2216; https://doi.org/10.3390/math13132216 - 7 Jul 2025
Viewed by 444
Abstract
Failure Mode and Effects Analysis (FMEA) is a proactive management technique widely used to improve the reliability of products and processes across various business sectors. Due to rapid changes stemming from uncertain environments, numerous studies have proposed different approaches to enhance the effectiveness [...] Read more.
Failure Mode and Effects Analysis (FMEA) is a proactive management technique widely used to improve the reliability of products and processes across various business sectors. Due to rapid changes stemming from uncertain environments, numerous studies have proposed different approaches to enhance the effectiveness of the FMEA method. However, there is a lack of systematic literature reviews and classification of research on this topic. The purpose of this paper is to systematically review the literature on the integration of FMEA with Multi-Attribute Decision-Making (MADM) theories and various mathematical models. This study analyses a total of 68 papers published between 2015 and 2024, selected from 51 peer-reviewed journals indexed in Scopus and/or Web of Science. Furthermore, a bibliometric analysis was conducted based on the frequency of different mathematical theories used to model existing uncertainties, methods for determining the weighting vectors of risk factors (RFs), the use of MADM theories extended with uncertain numbers for weighting RFs and prioritizing identified failure modes, publication years, journals, and application domains. This research aims to support both researchers and practitioners in effectively adopting uncertain MADM methods to address the limitations of traditional FMEA and provide insight into the current state of the art in this field. Full article
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18 pages, 1870 KiB  
Article
Flowering and Morphology Responses of Greenhouse Ornamentals to End-of-Day Blue-Dominant Lighting with Different Phytochrome Photostationary States
by Yun Kong, Qingming Li, David Llewellyn and Youbin Zheng
Agronomy 2025, 15(7), 1649; https://doi.org/10.3390/agronomy15071649 - 7 Jul 2025
Viewed by 272
Abstract
To investigate whether blue-dominant spectra from end-of-day (EOD) lighting can regulate crop morphological and flowering responses, chrysanthemum (Chrysanthemum × morifolium; obligate short day), geranium (Pelargonium × hortorum; day neutral), calibrachoa (Calibrachoa × hybrida; facultative long day), and gerbera ( [...] Read more.
To investigate whether blue-dominant spectra from end-of-day (EOD) lighting can regulate crop morphological and flowering responses, chrysanthemum (Chrysanthemum × morifolium; obligate short day), geranium (Pelargonium × hortorum; day neutral), calibrachoa (Calibrachoa × hybrida; facultative long day), and gerbera (Gerbera jamesonii; facultative short day) plants were grown under different light-emitting diode (LED) spectrum treatments from January to April 2020, in Guelph, Canada. The spectrum treatments were (1) no EOD lighting, (2) narrowband blue from LEDs (B), (3) a combination of narrowband blue, red, and far-red LEDs with a photon flux ratio of 47:3:1 (blue:red:far-red; BRFR). The B and BRFR treatments ran daily from 0.5 h to 4.5 h after dusk. Compared to the control without EOD lighting, chrysanthemum flower initiation was completely inhibited under BRFR. Flowering time was slightly delayed, but flower bud number increased under B. Side branch number, leaf area, and main stem length and diameter increased under B and BRFR. In the geranium B and BRFR did not affect flowering, but increased side branch number and length and diameter of the main stem. Both spectrum treatments promoted earlier flowering in the calibrachoa, but BRFR produced more flower buds. The calibrachoa aerial dry biomass and main stem length increased under B and BRFR. The gerbera leaf chlorophyll index and leaf thickness increased under BRFR. Both spectrum treatments increased the gerbera flower bud size, despite having little effect on flowering time. In all species, at least one of the LED treatments increased canopy size. Therefore, low levels of B or BRFR can be potentially used for EOD lighting to regulate the flowering and morphology of potted ornamentals. Full article
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23 pages, 11218 KiB  
Article
Serotonin N-acetyltransferase SlSNAT2 Positively Regulates Tomato Resistance Against Ralstonia solanacearum
by Yixi Wang, Gengshou Xia, Xinyi Xie, Hao Wang, Lingyun Zheng, Zhijie He, Junxian Ye, Kangtong Xu, Qi Shi, Hui Yang and Yan Zhang
Int. J. Mol. Sci. 2025, 26(13), 6530; https://doi.org/10.3390/ijms26136530 - 7 Jul 2025
Viewed by 335
Abstract
Bacterial wilt (BW) is a globally serious soil-borne disease in a wide range of plants, caused by diverse strains of Ralstonia solanacearum. However, there are few research reports on melatonin regulating plant resistance against R. solanacearum. N-acetyltransferase SlSNAT2 is a [...] Read more.
Bacterial wilt (BW) is a globally serious soil-borne disease in a wide range of plants, caused by diverse strains of Ralstonia solanacearum. However, there are few research reports on melatonin regulating plant resistance against R. solanacearum. N-acetyltransferase SlSNAT2 is a rate-limiting enzyme in plant melatonin synthesis. This study elucidates the mechanisms of SlSNAT2 modulating tomato resistance to BW. SlSNAT2 was expressed in tomato roots, stems, and leaves and induced upon R. solanacearum inoculation. Knocking out SlSNAT2 significantly decreased the melatonin content in CRISPR/Cas9 mutant slsnat2. With R. solanacearum inoculation, the morbidity and disease index value of slsnat2 were significantly higher than those of the tomato wild-type plant Micro-Tom (MT) according to the wilt rate and severity. The chlorophyll levels, photosynthetic rates, and callus deposition quantity in slsnat2 were notably lower while the reactive oxygen species (ROS) level was considerably higher than those in the MT after inoculation. Additionally, the SlSNAT2 deficiency depressed the expression of the mitogen-activated protein kinase (MAPK) pathway genes (SlMPK1, SlMKK2), salicylic acid pathway genes (SlGluA, SlPR-1a), jasmonic acid pathway gene SlPin2, and pathogenesis-related (PR) protein genes (SlPR-STH2a, SlPR-STH2b, SlPR-STH2c, SlPR-STH2d). These results revealed SlSNAT2 enhanced the tomato resistance against R. solanacearum by orchestrating ROS homeostasis, callose deposition, MAPK signaling, hormone pathways, and PR gene transcripts. Full article
(This article belongs to the Section Molecular Plant Sciences)
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15 pages, 1019 KiB  
Article
Genotypic Variability in Growth and Leaf-Level Physiological Performance of Highly Improved Genotypes of Pinus radiata D. Don Across Different Sites in Central Chile
by Sergio Espinoza, Marco Yáñez, Carlos Magni, Eduardo Martínez-Herrera, Karen Peña-Rojas, Sergio Donoso, Marcos Carrasco-Benavides and Samuel Ortega-Farias
Forests 2025, 16(7), 1108; https://doi.org/10.3390/f16071108 - 4 Jul 2025
Viewed by 208
Abstract
Pinus radiata D. Don is planted in South Central Chile on a wide range of sites using genetically improved genotypes for timber production. As drought events are expected to increase with ongoing climatic change, the variability in gas exchange, which could impact growth [...] Read more.
Pinus radiata D. Don is planted in South Central Chile on a wide range of sites using genetically improved genotypes for timber production. As drought events are expected to increase with ongoing climatic change, the variability in gas exchange, which could impact growth and water use, needs to be evaluated. In this study, we assessed the genotypic variability of leaf-level light-saturated photosynthesis (Asat), stomatal conductance (gs), transpiration (E), intrinsic water use efficiency (iWUE), and Chlorophyll a fluorescence (OJIP-test parameters) among 30 P. radiata genotypes (i.e., full-sib families) from third-cycle parents at age 6 years on three sites in Central Chile. We also evaluated tree height (HT), diameter at breast height (DBH), and stem index volume (VOL). Families were ranked for HT as top-15 and bottom-15. In the OJIP-test parameters we observed differences at the family level for the maximum quantum yield of primary PSII photochemistry (Fv/Fm), the probability that a photon trapped by the PSII reaction center enters the electron transport chain (ψEo), and the potential for energy conservation from photons captured by PSII to the reduction in intersystem electron acceptors (PIABS). Fv/Fm, PIABS, and ψEo ranged from 0.82 to 0.87, 45 to 95, and 0.57 to 0.64, respectively. Differences among families for growth and not for leaf-level physiology were detected. DBT, H, and VOL were higher in the top-15 families (12.6 cm, 8.4 m, and 0.10 m3, respectively) whereas Asat, gs, E, and iWUE were similar in both the top-15 and bottom-15 families (4.0 μmol m−2 s−1, 0.023 mol m−2 s−1, 0.36 mmol m−2 s−1, and 185 μmol mol m−2 s−1, respectively). However, no family by site interaction was detected for growth and leaf-level physiology. The results of this study suggest that highly improved genotypes of P. radiata have uniformity in leaf-level physiological rates, which could imply uniform water use at the stand-level. The family variation found in PIABS suggests that this parameter could be incorporated to select genotypes tolerant to environmentally stressful conditions. Full article
(This article belongs to the Special Issue Water Use Efficiency of Forest Trees)
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17 pages, 4939 KiB  
Article
Wood Loss in the Felling and Cross-Cutting of Trees from Spruce Stands Affected by Windthrow in the Curvature Carpathians
by Mihai Ciocirlan and Vasile Răzvan Câmpu
Forests 2025, 16(7), 1102; https://doi.org/10.3390/f16071102 - 3 Jul 2025
Viewed by 250
Abstract
Windthrow determines major changes in tree stand evolution due to the felling or breaking of either isolated trees or entire stands. It has a major ecological, social and economic impact. Wood loss resulting from tree felling and cross-cutting operations is a less-studied aspect [...] Read more.
Windthrow determines major changes in tree stand evolution due to the felling or breaking of either isolated trees or entire stands. It has a major ecological, social and economic impact. Wood loss resulting from tree felling and cross-cutting operations is a less-studied aspect related to windthrow. Wood loss is represented by high stumps, broken or split stems, wood lost in the felling of trees that remain standing, wood lost in felling cuts that attempt to remove the stem from the root plate of partially or totally uprooted trees and wood lost as a result of stem cross-cutting. The study focused on estimating losses and their indices in a spruce tree stand located in the Curvature Carpathians. Windthrow took place in this tree stand in February 2020. The results showed that the total wood loss index is 7.747%. The main losses are represented by wood losses in high stumps (5.319%). The amount of wood loss depends on the proportion of uprooted or standing trees, ground inclination and the uprooting direction of trees as opposed to ground inclination, as well as on tree dimension. Tree volume significantly influences wood loss in high stumps (p < 0.001). The closer the uprooting direction is to the highest slope, the higher the tree stump becomes. Wood loss caused by stem breaking and splitting represents 2.280%, tree felling cuttings and stem removal from the root plate in uprooted trees account for 0.138% while loss resulting from stem cross-cutting represents 0.10%. Full article
(This article belongs to the Special Issue Sustainable Forest Operations Planning and Management)
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26 pages, 7559 KiB  
Article
A Meta-Frontier Approach to Evaluating the Environmental Efficiency of Coastal Ports: Implications for Port Sustainability
by Gaofeng Gu, Jiewei Zhang and Xiaofeng Pan
J. Mar. Sci. Eng. 2025, 13(7), 1272; https://doi.org/10.3390/jmse13071272 - 30 Jun 2025
Viewed by 338
Abstract
As pivotal nodes in maritime logistics networks, ports face mounting pressure to reconcile economic growth with environmental sustainability. Although the SBM-Undesirable model has been extensively applied to assess port environmental efficiency (PEE), most applications assume strong disposability and disregard heterogeneity in technological capacities [...] Read more.
As pivotal nodes in maritime logistics networks, ports face mounting pressure to reconcile economic growth with environmental sustainability. Although the SBM-Undesirable model has been extensively applied to assess port environmental efficiency (PEE), most applications assume strong disposability and disregard heterogeneity in technological capacities across different port scales, potentially biasing the assessments. To overcome these limitations, coastal ports are initially categorized into three subgroups based on operational scale criteria. A meta-frontier SBM-Undesirable model incorporating weak disposability is then developed to evaluate PEE. Dynamic characteristics are further explored via the Global Malmquist Index. Results indicate substantial disparities between subgroup frontiers and the meta-frontier. The average group PEE (0.732) exceeded the meta PEE (0.570), implying potential overestimation under homogeneity assumptions. Large-sized ports, with a mean technology gap ratio (TGR) of 0.956, operated near the meta-frontier, whereas medium-sized and small-sized ports, with TGRs of 0.770 and 0.600 respectively, exhibited substantial technological gaps. Total factor productivity (TFP) demonstrated a volatile upward trend, averaging 6.8% annual growth. In large-sized and medium-sized ports, TFP growth was primarily driven by technological innovation, whereas in small-sized ports, it stemmed from combined improvements in technical efficiency and technological level. These insights underscore the necessity of differentiated decarbonization strategies for port management. Full article
(This article belongs to the Special Issue Maritime Transport and Port Management)
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24 pages, 1404 KiB  
Review
Hippocampal Neurogenesis in Alzheimer’s Disease: Multimodal Therapeutics and the Neurogenic Impairment Index Framework
by Li Ma, Qian Wei, Ming Jiang, Yanyan Wu, Xia Liu, Qinghu Yang, Zhantao Bai and Liang Yang
Int. J. Mol. Sci. 2025, 26(13), 6105; https://doi.org/10.3390/ijms26136105 - 25 Jun 2025
Viewed by 529
Abstract
Alzheimer’s disease (AD) is characterized by progressive cognitive decline strongly associated with impaired adult hippocampal neurogenesis (AHN). Mounting evidence suggests that this impairment results from both the intrinsic dysfunction of neural stem cells (NSCs)—such as transcriptional alterations in quiescent states—and extrinsic niche disruptions, [...] Read more.
Alzheimer’s disease (AD) is characterized by progressive cognitive decline strongly associated with impaired adult hippocampal neurogenesis (AHN). Mounting evidence suggests that this impairment results from both the intrinsic dysfunction of neural stem cells (NSCs)—such as transcriptional alterations in quiescent states—and extrinsic niche disruptions, including the dysregulation of the Reelin signaling pathway and heightened neuroinflammation. Notably, AHN deficits may precede classical amyloid-β and Tau pathology, supporting their potential as early biomarkers of disease progression. In this review, we synthesize recent advances in therapeutic strategies aimed at restoring AHN, encompassing pharmacological agents, natural products, and non-pharmacological interventions such as environmental enrichment and dietary modulation. Emerging approaches—including BDNF-targeted nanocarriers, NSC-derived extracellular vesicles, and multimodal lifestyle interventions—highlight the translational promise of enhancing neurogenesis in models of familial AD. We further propose the Neurogenesis Impairment Index (NII)—a novel composite metric that quantifies hippocampal neurogenic capacity relative to amyloid burden, while adjusting for demographic and cognitive variables. By integrating neurogenic potential, cognitive performance, and pathological load, NII provides a framework for stratifying disease severity and guiding personalized therapeutic approaches. Despite ongoing challenges—such as interspecies differences in neurogenesis rates and the limitations of stem cell-based therapies—this integrative perspective offers a promising avenue to bridge mechanistic insights with clinical innovation in the development of next-generation AD treatments. Full article
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15 pages, 868 KiB  
Review
Hematopoietic Stem Cell Transplant in Adult Patients with Fanconi Anemia: A Review
by Bradley Rockwell, Prakriti Ramamurthy, Jhannine Alyssa Verceles, Amanda Lombardo, Amit Verma and Dennis L. Cooper
Diseases 2025, 13(7), 195; https://doi.org/10.3390/diseases13070195 - 25 Jun 2025
Viewed by 415
Abstract
Fanconi anemia (FA) is characterized by faulty DNA repair and is associated with bone marrow failure, acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS). Because of the more widespread use of next-generation sequencing (NGS) and increased testing for germline mutations in young patients [...] Read more.
Fanconi anemia (FA) is characterized by faulty DNA repair and is associated with bone marrow failure, acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS). Because of the more widespread use of next-generation sequencing (NGS) and increased testing for germline mutations in young patients with MDS and AML, FA is increasingly being first diagnosed in adults, many of whom lack classical physical stigmata. Hematopoietic stem cell transplant is the only cure for the hematologic manifestations of FA but there are several unique considerations in FA patients, including first maintaining a high index of suspicion for the diagnosis in patients with minimal phenotypic abnormalities, second an exaggerated sensitivity to alkylating agents and radiation, precluding the use of standard myeloablative conditioning regimens despite the young age of most of the patients, and lastly a marked propensity for squamous cell cancers of the upper aerodigestive tract and anogenital region, likely further increased by the drugs used in conditioning and by chronic inflammation in patients who develop graft-versus-host disease. Despite a growing number of FA patients surviving into adulthood or first being diagnosed with FA as an adult, there is minimal literature describing transplant methodology and outcomes. In the following case-based review of a patient, we incorporate recent findings from the literature on the care of this challenging patient population. Full article
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14 pages, 1780 KiB  
Systematic Review
Effects of Prenatal Arsenic, Cadmium, and Manganese Exposure on Neurodevelopment in Children: A Systematic Review and Meta-Analysis
by Rui Su, Yi Jiang, Weikun Li, Wencheng Ding and Ling Feng
Medicina 2025, 61(7), 1143; https://doi.org/10.3390/medicina61071143 - 25 Jun 2025
Viewed by 276
Abstract
Objective: The aim of this study was to investigate the effects of prenatal heavy metal (arsenic, cadmium, manganese) exposure on infant neurodevelopment through a systematic review and meta-analysis, elucidating the toxicological mechanisms and dose–response relationships for consideration in environmental risk assessment. Methods [...] Read more.
Objective: The aim of this study was to investigate the effects of prenatal heavy metal (arsenic, cadmium, manganese) exposure on infant neurodevelopment through a systematic review and meta-analysis, elucidating the toxicological mechanisms and dose–response relationships for consideration in environmental risk assessment. Methods: Following the PRISMA guidelines, systematic searches were conducted in PubMed, Embase, and other databases, ultimately resulting in 17 observational studies involving 6907 participants. Results: Arsenic (As): A 50% increase in arsenic exposure was associated with a reduction of 0.51 points in the Mental Development Index (MDI; 95% CI: −1.43 to 0.4) and 0.15 points in the Psychomotor Development Index (PDI; 95% CI: −0.96 to 0.65). However, these results did not achieve statistical significance (p > 0.05). Cadmium (Cd): Prenatal cadmium exposure significantly decreased the Full-Scale Intelligence Quotient (FSIQ) in children aged 5–9 years. A 50% increase in cadmium exposure resulted in a 0.44-point drop in the FSIQ (95% CI: −0.67 to −0.21, p < 0.05), with stable effects (I2 = 0%). Manganese (Mn): Manganese exposure showed a negative association with the MDI (β = −0.11) and PDI (β = −0.18). However, a high degree of heterogeneity was observed (I2 = 20.89–73.35%), and some studies suggested potential risks even at low exposure levels. Sensitivity analyses indicated that the heterogeneity in the arsenic and manganese results mainly stemmed from individual study differences (e.g., sample characteristics), whereas the cadmium effects were consistent. Conclusions: Prenatal heavy metal exposure (notably cadmium) adversely impacts neurodevelopment, even at low doses. Future research should prioritize critical exposure windows, mixed effects, and sex-specific vulnerabilities. Strengthening environmental monitoring and prenatal guidelines is crucial to mitigate developmental risks. Full article
(This article belongs to the Section Obstetrics and Gynecology)
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16 pages, 3298 KiB  
Article
A Novel Pathogenic Variant Identified in HIKESHI-Related Hypomyelinating Leukodystrophy Disrupts Heat Shock Response in iPSCs
by Mahmood Ali Saleh, Maria Boichuck, Aner Ottolenghi, Tatiana Rabinski, Omri Goldenthal, Daniel Sevilla Sanchez, Aviva Fattal-Valevski, Gali Heimer, Shay Ben-Shachar, Stephanie Libzon, Orly Gershoni-Yahalom, Anat Ben-Zvi, Raz Zarivach, Ayelet Zerem, Benyamin Rosental and Gad David Vatine
Int. J. Mol. Sci. 2025, 26(13), 6037; https://doi.org/10.3390/ijms26136037 - 24 Jun 2025
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Abstract
HIKESHI-related hypomyelinating leukodystrophy (HHL) is a life-threatening disorder caused by homozygous pathogenic variants in HIKESHI. Symptoms include infantile onset progressive spastic dystonic quadriplegia, nystagmus, failure to thrive, diffused hypomyelination, and severe morbidity or death following febrile illness. V54L variants in HIKESHI are [...] Read more.
HIKESHI-related hypomyelinating leukodystrophy (HHL) is a life-threatening disorder caused by homozygous pathogenic variants in HIKESHI. Symptoms include infantile onset progressive spastic dystonic quadriplegia, nystagmus, failure to thrive, diffused hypomyelination, and severe morbidity or death following febrile illness. V54L variants in HIKESHI are particularly prevalent within the Ashkenazi Jewish population. Here, we identified a novel P78S disease-causing variant in HIKESHI in a patient of Christian Arab origin, presenting with clinical and radiologic features characteristic of HHL. In silico analysis suggests that the mutated residue may affect the HIKESHI protein’s dimerization domain. We generated a comprehensive set of induced pluripotent stem cells (iPSCs) from the index case and two additional HHL patients. To investigate mechanisms potentially linked to febrile illness in HHL, we used these cells to study the heat shock (HS) response. HHL-iPSCs showed dramatically decreased levels of HIKESHI compared with healthy controls following HS. In addition, they exhibited increased HSP70 mRNA levels in response to HS, suggesting an increased sensitivity. HHL-iPSCs had impaired HSP70 translocation to the nucleus. Our results provide a human-relevant model for HHL. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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