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20 pages, 994 KB  
Perspective
Endocrinology and the Lung: Exploring the Bidirectional Axis and Future Directions
by Pedro Iglesias
J. Clin. Med. 2025, 14(19), 6985; https://doi.org/10.3390/jcm14196985 - 2 Oct 2025
Abstract
The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors [...] Read more.
The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors and secrete mediators with both local and systemic effects, defining the concept of the “endocrine lung”. This narrative review summarizes current evidence on the endocrine–pulmonary axis. Thyroid hormones, glucocorticoids, sex steroids, and metabolic hormones (e.g., insulin, leptin, adiponectin) critically influence alveologenesis, surfactant production, ventilatory drive, airway mechanics, and immune responses. Conversely, the lung produces mediators such as serotonin, calcitonin gene-related peptide, endothelin-1, leptin, and keratinocyte growth factor, which regulate vascular tone, alveolar homeostasis, and immune modulation. We also describe the respiratory manifestations of major endocrine diseases, including obstructive sleep apnea and lung volume alterations in acromegaly, immunosuppression and myopathy in Cushing’s syndrome, hypoventilation in hypothyroidism, restrictive “diabetic lung”, and obesity-related phenotypes. In parallel, chronic pulmonary diseases such as chronic obstructive pulmonary disease, interstitial lung disease, and sleep apnea profoundly affect endocrine axes, promoting insulin resistance, hypogonadism, GH/IGF-1 suppression, and bone metabolism alterations. Pulmonary neuroendocrine tumors further highlight the interface, frequently presenting with paraneoplastic endocrine syndromes. Finally, therapeutic interactions are discussed, including the risks of hypothalamic–pituitary–adrenal axis suppression with inhaled corticosteroids, immunotherapy-induced endocrinopathies, and inhaled insulin. Future perspectives emphasize mapping pulmonary hormone networks, endocrine phenotyping of chronic respiratory diseases, and developing hormone-based interventions. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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22 pages, 6066 KB  
Article
Genome-Wide Identification and Analysis of Chitinase GH18 Gene Family in Trichoderma longibrachiatum T6 Strain: Insights into Biocontrol of Heterodera avenae
by Cizhong Duan, Jia Liu, Shuwu Zhang and Bingliang Xu
J. Fungi 2025, 11(10), 714; https://doi.org/10.3390/jof11100714 - 1 Oct 2025
Abstract
The cereal cyst nematode, Heterodera avena, is responsible for substantial economic losses in the global production of wheat, barley, and other cereal crops. Extracellular enzymes, particularly those from the glycoside hydrolase 18 (GH18) family, such as chitinases secreted by Trichoderma spp., play [...] Read more.
The cereal cyst nematode, Heterodera avena, is responsible for substantial economic losses in the global production of wheat, barley, and other cereal crops. Extracellular enzymes, particularly those from the glycoside hydrolase 18 (GH18) family, such as chitinases secreted by Trichoderma spp., play a crucial role in nematode control. However, the genome-wide analysis of Trichoderma longibrachiatum T6 (T6) GH18 family genes in controlling of H. avenae remains unexplored. Through phylogenetic analysis and bioinformatics tools, we identified and conducted a detailed analysis of 18 GH18 genes distributed across 13 chromosomes. The analysis encompassed gene structure, evolutionary development, protein characteristics, and gene expression profiles following T6 parasitism on H. avenae, as determined by RT-qPCR. Our results indicate that 18 GH18 members in T6 were clustered into three major groups (A, B, and C), which comprise seven subgroups. Each subgroup exhibits highly conserved catalytic domains, motifs, and gene structures, while the cis-acting elements demonstrate extensive responsiveness to hormones, stress-related signals, and light. These members are significantly enriched in the chitin catabolic process, extracellular region, and chitinase activity (GO functional enrichment), and they are involved in amino sugar and nucleotide sugar metabolism (KEGG pathway enrichment). Additionally, 13 members formed an interaction network, enhancing chitin degradation efficiency through synergistic effects. Interestingly, 18 members of the GH18 family genes were expressed after T6 parasitism on H. avenae cysts. Notably, GH18-3 (Group B) and GH18-16 (Group A) were significantly upregulated, with average increases of 3.21-fold and 3.10-fold, respectively, from 12 to 96 h after parasitism while compared to the control group. Meanwhile, we found that the GH18-3 and GH18-16 proteins exhibit the highest homology with key enzymes responsible for antifungal activity in T. harzianum, demonstrating dual biocontrol potential in both antifungal activity and nematode control. Overall, these results indicate that the GH18 family has undergone functional diversification during evolution, with each member assuming specific biological roles in T6 effect on nematodes. This study provides a theoretical foundation for identifying novel nematicidal genes from T6 and cultivating highly efficient biocontrol strains through transgenic engineering, which holds significant practical implications for advancing the biocontrol of plant-parasitic nematodes (PPNs). Full article
(This article belongs to the Section Fungal Genomics, Genetics and Molecular Biology)
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24 pages, 2318 KB  
Article
From Chaos to Coherent Structure (Pattern): The Mathematical Architecture of Invisible Time—The Critical Minute Theorem in Ground Handling Operations in an Aircraft Turnaround on the Ground of an Airport
by Cornel Constantin Tuduriu, Dan Laurentiu Milici and Mihaela Paval
Logistics 2025, 9(4), 139; https://doi.org/10.3390/logistics9040139 - 1 Oct 2025
Abstract
Background: In the dynamic world of commercial aviation, the efficient management of ground handling (GH) operations in aircraft turnarounds is an increasingly complex challenge, often perceived as operational chaos. Methods: This paper introduces the “Critical Minute Theorem” (CMT), a novel framework [...] Read more.
Background: In the dynamic world of commercial aviation, the efficient management of ground handling (GH) operations in aircraft turnarounds is an increasingly complex challenge, often perceived as operational chaos. Methods: This paper introduces the “Critical Minute Theorem” (CMT), a novel framework that integrates mathematical architecture principles into the optimization of GH processes. CMT identifies singular temporal thresholds, tk* at which small local disturbances generate nonlinear, system-wide disruptions. Results: By formulating the turnaround as a set of algebraic dependencies and nonlinear differential relations, the case studies demonstrate that delays are not random but structurally determined. The practical contribution of this study lies in showing that early recognition and intervention at these critical minutes significantly reduces propagated delays. Three case analyses are presented: (i) a fueling delay initially causing 9 min of disruption, reduced to 3.7 min after applying CMT-based reordering; (ii) baggage mismatch scenarios where CMT-guided list restructuring eliminates systemic deadlock; and (iii) PRM assistance delays mitigated by up to 12–15 min through anticipatory task reorganization. Conclusions: These results highlight that CMT enables predictive, non-technological control in turnaround operations, repositioning the human analyst as an architect of time capable of restoring structure where the system tends to collapse. Full article
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18 pages, 3197 KB  
Article
Weight Gain and Tenderness in Nelore Cattle: Genetic Association and a Potential Pleiotropic Role of Transcription Factors and Genes
by Elora R. P. de S. Borges, Lucio F. M. Mota, Lucas L. Verardo, Lucia G. de Albuquerque, Marcela R. Duarte, Geovana C. Santos, Alice S. Pereira, Lorena M. P. de Carvalho, Lilia S. Carvalho, Emily A. R. Almeida and Ana F. B. Magalhães
Animals 2025, 15(19), 2874; https://doi.org/10.3390/ani15192874 - 30 Sep 2025
Abstract
The inclusion of meat quality traits in breeding programs is a promising strategy to improve beef by selecting animals based on both growth and meat quality. This study aimed to estimate genetic parameters for average daily gain (ADG) and Warner–Bratzler shear force (WBSF), [...] Read more.
The inclusion of meat quality traits in breeding programs is a promising strategy to improve beef by selecting animals based on both growth and meat quality. This study aimed to estimate genetic parameters for average daily gain (ADG) and Warner–Bratzler shear force (WBSF), as well as to perform genome-wide association studies (GWAS) to identify genomic regions and transcription factor (TF) binding sites associated with both traits in Nelore cattle. Genetic parameters were estimated using a bi-trait Bayesian model, and GWAS identified key SNPs explaining over 1% of variance in genomic estimated breeding values. Candidate genes near these SNPs were annotated, TF binding sites predicted, and gene–TF networks constructed. Genetic estimates indicated moderate heritability for ADG, low heritability for WBSF, and a small negative genetic correlation between traits. Genomic regions contained 116 and 151 candidate genes for ADG and WBSF, respectively, with 35 shared between traits. Functional analyses highlighted MYBPC1 and PENK for WBSF, and GHRS and NPY for ADG. TF analysis identified 25 TFs, with 3 key ones highlighted. Gene–TF networks revealed candidates including CAPN1 and LTBP3 for WBSF, and CARM1 and GH1 for ADG. Shared candidate genes identified in the combined network provide valuable insights into the genetic architecture of growth and tenderness in Nelore cattle. Full article
(This article belongs to the Special Issue Livestock Omics)
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17 pages, 1115 KB  
Article
Directed Evolution of Xylanase from Dickeya dadantii DCE-01 with Improved Enzymatic Activity
by Ruijun Wang, Ke Shi, Ke Zheng, Qi Yang, Guoguo Xi, Shengwen Duan and Lifeng Cheng
Polymers 2025, 17(19), 2650; https://doi.org/10.3390/polym17192650 - 30 Sep 2025
Abstract
Xylanase, an essential enzyme for breaking down xylan, faces limitations in its industrial applications due to the relatively low catalytic activity of the wild type. Directed evolution was used to enhance the catalytic efficiency of xylanase that originated from the Dickeya dadantii DCE-01. [...] Read more.
Xylanase, an essential enzyme for breaking down xylan, faces limitations in its industrial applications due to the relatively low catalytic activity of the wild type. Directed evolution was used to enhance the catalytic efficiency of xylanase that originated from the Dickeya dadantii DCE-01. A xylanase variant (Xyn-ep) was obtained with improved catalytic activity by random mutant library employing two rounds of error-prone PCR. The results showed that the Xyn-ep demonstrated enzyme activity 1.6 times higher than that of wild-type xylanase. Sequencing analysis pinpointed key mutation sites at S159P, K212N, and N397S, respectively. Homology modeling was used to analyze the location of the mutation sites and to investigate the mechanism of the improved catalytic performance. The mutant Xyn-ep showed improved catalytic performance by error-prone PCR. Additionally, the increased flexibility of the loop of the mutant may contribute to the enhanced activity. These findings indicate that error-prone PCR is an effective method for enhancing enzyme activity and that the mutant Xyn-ep may be a new GH30 xylanase, being a potential candidate for industrial applications such as bast fiber bio-degumming, cotton bio-refinery, paper making, and so on. Full article
21 pages, 8013 KB  
Article
Immunoproteomic Screening of Candidate Antigens for the Preliminary Development of a Novel Multi-Component and Multi-Epitope Vaccine Against Streptococcus suis Infection
by Yue Zhang, Caiying Li, Yutong Feng, Qibing Gu, Jinwang Hu, Yuhang Li, Lu Xia and Shaopo Zu
Vaccines 2025, 13(10), 1020; https://doi.org/10.3390/vaccines13101020 - 30 Sep 2025
Abstract
Background/Objectives: Streptococcus suis (SS), an important zoonotic pathogen, has caused significant economic losses to the global pig industry. Existing commercial vaccines for SS mainly provide effective protection against a single serotype. Due to the existence of many serotypes and their robust immune [...] Read more.
Background/Objectives: Streptococcus suis (SS), an important zoonotic pathogen, has caused significant economic losses to the global pig industry. Existing commercial vaccines for SS mainly provide effective protection against a single serotype. Due to the existence of many serotypes and their robust immune evasion capabilities, the development of multi-component subunit vaccines or multi-epitope vaccines that provide effective cross-protection against different strains of SS is a key focus of current research. Methods: We applied two-dimensional electrophoresis (2-DE) and immunoblotting to screen for candidate immunogens among the immunogenic cell wall proteins of SS. BALB/c mice were immunized intradermally with a multi-component, multi-epitope vaccine. The vaccine’s safety and immunogenicity were assessed via clinical monitoring, antibody titer detection, cytokine assays, and survival curve analyses. Results: In this study, eight immunogenic cell wall proteins (GH25, Pk, PdhA, Ldh, ExoA, Pgk, MalX, and Dnak) were successfully identified using MALDI-TOF-MS, all of which could induce high IgG antibody titers. Based on the conservation and immunoprotection demonstrated by these eight protective antigenic proteins, PdhA, Ldh, and MalX were screened to construct a multi-component subunit vaccine as a candidate vaccine for providing cross-protection against SS isolates of multiple serotypes. Challenge studies showed that mice immunized with the multi-component subunit vaccine (PdhA, Ldh, and MalX) were protected against challenges with the SS2 virulent strain ZY05719 (62.5% protection) and the SSChz virulent strain CZ130302 (75% protection). Subsequently, we utilized immunoinformatics techniques to design a novel multi-epitope vaccine (MVPLM) derived from the immunogenic proteins PdhA, Ldh, and MalX. However, challenge tests revealed that the MVPLM offered limited protection against SS. Conclusions: These data demonstrate that a multi-component subunit vaccine composed of PdhA, Ldh, and MalX proteins shows promise as a candidate universal vaccine against multiple SS serotypes. Full article
(This article belongs to the Special Issue Vaccines for Porcine Viruses)
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13 pages, 1595 KB  
Article
Differential Plasma Carotenoid Profiles in Hypertensive Disorders of Pregnancy
by Colman I. Freel, Jonah Scheffler, Rebecca A. Drakowski, Elizabeth Lyden, Matthew VanOrmer, Melissa K. Thoene, Paras Kumar Mishra, Corrine K. Hanson and Ann L. Anderson-Berry
Nutrients 2025, 17(19), 3104; https://doi.org/10.3390/nu17193104 - 29 Sep 2025
Abstract
Background: Hypertensive disorders of pregnancy (HDP) affect one in six pregnancies globally. The etiology of HDP remains unclear but is known to involve oxidative stress. While the body produces endogenous antioxidants, antioxidative nutrients, like carotenoids, remain critical in modulating oxidative stress. The [...] Read more.
Background: Hypertensive disorders of pregnancy (HDP) affect one in six pregnancies globally. The etiology of HDP remains unclear but is known to involve oxidative stress. While the body produces endogenous antioxidants, antioxidative nutrients, like carotenoids, remain critical in modulating oxidative stress. The statuses of several carotenoids have been linked to hypertension in both pregnant and non-pregnant populations. However, their associations with the spectrum of HDP, including gestational hypertension (GH), chronic hypertension (CH), and preeclampsia (PE), remains unclear. Our objective was to quantify and compare carotenoid intake and plasma levels among HDP. Methods: We conducted a prospective cohort study of patients presenting for delivery at a Midwestern academic medical center between 2015 and 2023. Women ≥ 19 years old delivering at least one infant were eligible for inclusion. Mothers with diseases affecting nutrient metabolism or birthing newborn wards of the state were excluded. Subjects were recruited at delivery for Harvard Food Frequency Questionnaire and plasma sample collection. Plasma carotenoids were analyzed by HPLC-MS. Results: A total of 488 patients, including 270 normotensive (NT), 61 CH, 102 GH, and 55 PE, were recruited. Plasma carotenoid analyses were available for 225 subjects. Plasma total, cis-, and trans-β-carotene were significantly lower in PE (73 mcg/L) compared to NT (170 mcg/L), CH (194 mcg/L), and GH (190 mcg/L) groups. Lutein + zeaxanthin and β-cryptoxanthin were also reduced in PE (142 mcg/L and 81 mcg/L) compared to NT (209 mcg/L and 123 mcg/L) but only β-cryptoxanthin was lower in PE compared to GH (126 mcg/L). Levels of α-carotene were lower in PE (18 mcg/L) compared to both CH (43 mcg/L) and GH (48 mcg/L). Conclusions: These results demonstrate that plasma carotenoid levels differ among HDP and may suggest that oxidative stress in PE depletes circulating carotenoids, differentiating it from other HDP. Full article
(This article belongs to the Section Nutrition in Women)
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12 pages, 4294 KB  
Article
Overexpression of GhCAD6 in Upland Cotton (Gossypium hirsutum L.) Enhances Fiber Quality and Increases Lignin Content in Fibers
by Zumuremu Tuerxun, Chenyu Li, Xiaorong Li, Yuanxin Li, Xinxin Qin, Hui Zhang, Yang Yang, Guo Chen, Juan Li, Zhigang Liu, Xunji Chen, Darun Cai and Bo Li
Int. J. Mol. Sci. 2025, 26(19), 9518; https://doi.org/10.3390/ijms26199518 - 29 Sep 2025
Abstract
Cotton is a vital economic crop, and cotton fiber serves as the primary raw material for the textile industry. Lignin in cotton fiber is closely associated with fiber quality. Lignin is synthesized through the phenylpropanoid metabolic pathway, where the cinnamyl alcohol dehydrogenase gene [...] Read more.
Cotton is a vital economic crop, and cotton fiber serves as the primary raw material for the textile industry. Lignin in cotton fiber is closely associated with fiber quality. Lignin is synthesized through the phenylpropanoid metabolic pathway, where the cinnamyl alcohol dehydrogenase gene CAD6 plays a significant role. In this study, we obtained successfully transformed overexpression plants by constructing an overexpression vector and performing genetic transformation and tissue culture. To verify the function of the GhCAD6 gene in upland cotton, we analyzed the agronomic traits, fiber quality, cell wall structure, and lignin content of GhCAD6-overexpressing plants. Our results indicate that the GhCAD6 gene is predominantly expressed during the stages of fiber elongation and secondary wall synthesis. Overexpression of the GhCAD6 gene resulted in increased plant lignin content and fiber upper half mean length, boll number per plant, fiber uniformity index, strength, and lint were improved. The fiber surface was smoother, and the fiber cell wall was more compact. These findings demonstrate that the GhCAD6 gene positively regulates lignin synthesis and fiber quality formation, contributing to the enhancement of cotton fiber quality. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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13 pages, 659 KB  
Article
Retrieval Competition in Proactive Interference: Effects of Encoding Strength and Consolidation in the Modified Modified Free Recall Paradigm
by Yahui Zhang, Weihai Tang and Xiping Liu
Behav. Sci. 2025, 15(10), 1332; https://doi.org/10.3390/bs15101332 - 28 Sep 2025
Abstract
This study investigated how encoding strength and consolidation shape proactive interference (PI) in associative memory. Using a Modified Modified Free Recall (MMFR) paradigm, participants studied overlapping (A-B, A-C) and non-overlapping (E-F, G-H) pairs. The encoding strength of List 1 was manipulated (one vs. [...] Read more.
This study investigated how encoding strength and consolidation shape proactive interference (PI) in associative memory. Using a Modified Modified Free Recall (MMFR) paradigm, participants studied overlapping (A-B, A-C) and non-overlapping (E-F, G-H) pairs. The encoding strength of List 1 was manipulated (one vs. three study repetitions), while List 2 was held constant. Cued recall was tested immediately and after a 24-h delay. Results showed that increasing List 1’s encoding strength enhanced overall recall for both overlapping and non-overlapping pairs, indicating more effective learning, but did not alter the magnitude of PI. Instead, PI was strongly modulated by retention interval. At immediate test, robust PI emerged across conditions, reflecting cue-based retrieval competition. After a 24-h delay, PI was reduced or absent when List 1 was weakly encoded but persisted in attenuated form when List 1 was strongly encoded, suggesting differential consolidation trajectories for overlapping and non-overlapping associations. Co-retrieval analyses further revealed reliable associative dependency between B and C across all conditions, consistent with representational linkages that promote cooperative retrieval. These findings highlight the dual influence of cue overlap: at the representational level, overlapping pairs form integrated structures that foster co-retrieval, whereas at the retrieval-processing level, cue overload induces competition and PI. Taken together, the results indicate that although initial encoding strength enhances overall recall of List 2, the persistence of proactive interference is influenced by consolidation processes. Full article
(This article belongs to the Section Cognition)
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14 pages, 2279 KB  
Article
Development of KASP Molecular Markers and Candidate Gene Mining for Heat Tolerance-Related Traits in Gossypium hirsutum
by Zhaolong Gong, Ni Yang, Shiwei Geng, Juyun Zheng, Zhi Liu, Fenglei Sun, Shengmei Li, Xueyuan Li, Yajun Liang and Junduo Wang
Genes 2025, 16(10), 1154; https://doi.org/10.3390/genes16101154 - 28 Sep 2025
Abstract
Background: High-temperature stress is one of the major abiotic stresses limiting cotton production. Identifying genetic loci and genes for heat tolerance is crucial for breeding heat-tolerant varieties. Methods: Given the complexity of heat tolerance phenotypes in cotton, this study, which focused [...] Read more.
Background: High-temperature stress is one of the major abiotic stresses limiting cotton production. Identifying genetic loci and genes for heat tolerance is crucial for breeding heat-tolerant varieties. Methods: Given the complexity of heat tolerance phenotypes in cotton, this study, which focused on resource materials, identified an A/C SNP mutation at position 5486185 on chromosome D06 within the heat tolerance interval through genome-wide association studies (GWAS) of natural Gossypium hirsutum populations. Results: A total of 308 resource materials were identified and evaluated for their heat tolerance phenotypes over two years of field research. Kompetitive allele-specific PCR (KASP) molecular markers were developed on the basis of the D06-5486185 SNP to characterize the heat tolerance phenotypes of these 308 resource materials. Genotyping for heat tolerance-related traits and agronomic traits was also performed. Materials with the C/C haplotype at position D06-5486185 presented increased heat tolerance (higher pollen viability (PV), leaf area (LA), chlorophyll (Chl) and number of bolls on the third fruit branch (FB3) and a lower number of dry buds (DBs) and drop rate (DR)) without negatively impacting key yield traits. This locus is located in the intergenic region of two adjacent bZIP transcription factor genes (GH_D06G0408 and GH_D06G0409). Expression analysis revealed that the expression levels of these two genes were significantly greater in heat-tolerant accessions (C/C type) than in sensitive accessions and that their expression levels were significantly correlated with multiple heat-tolerant phenotypes. Conclusions: In summary, this study developed a Kompetitive Allele Specific PCR (KASP) marker associated with heat tolerance in G. hirsutum and identified two key heat tolerance candidate genes. These results provide an efficient marker selection tool and important genetic resources for the molecular breeding of heat-tolerant G. hirsutum, laying an important foundation for further establishing a molecular marker-assisted breeding system for heat tolerance in G. hirsutum. Full article
(This article belongs to the Special Issue Genetic Research on Crop Stress Resistance and Quality Traits)
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15 pages, 651 KB  
Systematic Review
Candidate Genes of Gastrointestinal Nematode Resistance Traits in Sheep: A Systematic Review of GWASs and Gene Prioritization Analysis
by Zhirou Zhang, Gang Liu, Deji Xu, Yueqi Ma, Xianlong Wang, Yong Wang, Lei Hou, Jiaqing Hu, Jianmin Wang and Tianle Chao
Genes 2025, 16(10), 1151; https://doi.org/10.3390/genes16101151 - 28 Sep 2025
Abstract
Background/Objectives: Gastrointestinal nematode infections represent a major constraint to sheep production globally, with widespread drug resistance requiring alternative control strategies. Methods: This systematic review combined genome-wide association study findings to understand the genetic basis underlying parasite resistance traits in sheep. Following PRISMA guidelines, [...] Read more.
Background/Objectives: Gastrointestinal nematode infections represent a major constraint to sheep production globally, with widespread drug resistance requiring alternative control strategies. Methods: This systematic review combined genome-wide association study findings to understand the genetic basis underlying parasite resistance traits in sheep. Following PRISMA guidelines, we identified 22 studies including 28,033 samples from 32 breeds across 11 countries, extracting 1580 candidate genes associated with resistance traits, including fecal egg count, packed cell volume, and immunoglobulin levels. Gene prioritization analysis using ToppGene identified 75 high-confidence candidate genes. Results: Functional enrichment analysis revealed significant involvement of the JAK-STAT signaling pathway, inflammatory response processes, and immune-related biological functions. Protein–protein interaction network analysis identified nine key hub genes: TNF, STAT3, STAT5A, PDGFB, ADRB2, MAPT, ITGB3, SMO, and GH1. The JAK-STAT pathway emerged as particularly important, with multiple core genes involved in cytokine signaling and immune cell development. These findings demonstrate that parasite resistance involves complex interactions between inflammatory responses, immune signaling networks, and metabolic processes. Conclusions: This comprehensive genetic framework provides essential insights for developing genomic selection strategies and marker-assisted breeding programs to enhance natural parasite resistance in sheep, offering a sustainable approach to reducing drug dependence and improving animal welfare in global sheep production systems. Full article
(This article belongs to the Special Issue Genetics and Breeding Improvements in Sheep and Goat)
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28 pages, 4396 KB  
Article
Kelulut Honey-Incorporated Hybrid Gelatin-PVA Hydrogel for Wound Healing: Fabrication and In Vitro Characterization
by Andik Nisa Zahra Zainuddin, Raniya Razif, Aifa Asyhira Khairul Nizam, Manira Maarof, Nur Izzah Md Fadilah, Yang-Hee Kim, Ebrahim Mahmoudi and Mh Busra Fauzi
Polymers 2025, 17(19), 2618; https://doi.org/10.3390/polym17192618 - 27 Sep 2025
Abstract
Hydrogels are attractive biomaterials for skin replacement and tissue regeneration, offering advantages over split-skin grafts for large or irregular wounds. Honey-containing hydrogels are of particular interest, combining honey’s natural healing properties with the versatility of hydrogel matrices. This study aimed to develop a [...] Read more.
Hydrogels are attractive biomaterials for skin replacement and tissue regeneration, offering advantages over split-skin grafts for large or irregular wounds. Honey-containing hydrogels are of particular interest, combining honey’s natural healing properties with the versatility of hydrogel matrices. This study aimed to develop a biocompatible, biodegradable, and mechanically stable hydrogel as a cutaneous substitute. To achieve this, different formulations were prepared using gelatin (GE), polyvinyl alcohol (PVA), and Kelulut honey (KH). The formulations were designated as: GE-PVA (6% (w/v) GE: 5% (w/v) PVA, without KH), GE-PVA-H1 (containing 1% (v/v) KH), GE-PVA-H5 (containing 5% (v/v) KH), and GE-PVA-H10 (containing 10% (v/v) KH). All formulations were crosslinked with 0.1% (w/v) genipin (GNP). GE-PVA-H1 and GE-PVA-H1-GNP showed swelling ratios of 110.18 ± 20.14% and 86.31 ± 14.27%, lower than GE-PVA-H5 (125.79 ± 23.76%), GE-PVA-H10 (132.79 ± 20.86%), and their crosslinked counterparts. All formulations had WVTR <1500 g/m−2h−1, with GE-PVA-H1-GNP at 501.21 ± 41.35 g/m−2h−1, GE-PVA-H5-GNP at 473.77 ± 44.10 g/m−2h−1, and GE-PVA-H10-GNP at 467.51 ± 73.59 g/m−2h−1. GE-PVA-H1-GNP exhibited the slowest biodegradation (0.0036 ± 0.0003 g/h vs. 0.0096–0.0206 g/h for other groups). Contact angle was lowest for GE-PVA-H1-GNP (38.46° ± 3.89°), confirming higher hydrophilicity compared with GE-PVA-H5/H10 groups. Resilience (98.85% ± 1.03%) and compression strength (77.42% ± 7.17%) of GE-PVA-H1-GNP were comparable to GE-PVA-H5-GNP and GE-PVA-H10-GNP. MTT assays confirmed cytocompatibility across all groups. Collectively, GE-PVA-H1-GNP emerged as the optimal formulation, combining mechanical stability, hydrophilicity, and biocompatibility for wound healing applications. Full article
(This article belongs to the Section Polymer Networks and Gels)
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22 pages, 12023 KB  
Article
Toxicological Assessment of Origanum majorana L.: Evaluation of Its Cytotoxicity, Genotoxicity, and Acute Oral Toxicity
by Ayfer Beceren, Ayse Nur Hazar-Yavuz, Ozlem Bingol Ozakpinar, Duygu Taskin, İsmail Senkardes, Turgut Taskin, Ozlem Tugce Cilingir-Kaya, Ahmad Kado and Hatice Kubra Elcioglu
Int. J. Mol. Sci. 2025, 26(19), 9461; https://doi.org/10.3390/ijms26199461 - 27 Sep 2025
Abstract
Medicinal plants remain central to traditional healthcare, yet their increasing integration into modern pharmacology necessitates robust toxicological evaluation. Origanum majorana L. (sweet marjoram), widely used in culinary and folk medicine, contains diverse secondary metabolites with both therapeutic and potential genotoxic activities. Despite its [...] Read more.
Medicinal plants remain central to traditional healthcare, yet their increasing integration into modern pharmacology necessitates robust toxicological evaluation. Origanum majorana L. (sweet marjoram), widely used in culinary and folk medicine, contains diverse secondary metabolites with both therapeutic and potential genotoxic activities. Despite its popularity, systematic in vivo and in vitro safety assessments remain limited. This study aimed to comprehensively evaluate the acute oral toxicity, cytotoxicity, and genotoxicity of O. majorana methanolic extract, providing baseline toxicological data to support its safe traditional use and potential pharmaceutical applications. The methanol extract of O. majorana leaves was tested in NIH-3T3 fibroblasts for cytotoxicity and genotoxicity. In vivo acute oral toxicity was assessed in rats according to OECD Guideline 420, with animals monitored over 14 days for clinical signs, hematological and biochemical alterations, and histopathological changes. The extract preserved fibroblast viability above 90% across all tested concentrations (10–200 µg/mL), indicating absence of cytotoxicity. However, comet and micronucleus assays revealed dose-dependent DNA damage, suggesting genotoxic potential at higher exposures. In vivo, no mortality or overt systemic toxicity was observed at doses up to 2000 mg/kg. Hematological analyses showed immunomodulatory shifts (increased neutrophils and monocytes, reduced eosinophils), while biochemical profiles indicated hepatoprotective and cardioprotective effects, with reduced ALT, AST, and LDH levels. Histopathological evaluation revealed only mild, focal changes consistent with adaptive rather than irreversible responses. O. majorana extract demonstrates a favorable acute safety profile with preserved hepatic and renal function, hematological modulation, and absence of in vitro cytotoxicity. Nevertheless, dose-dependent genotoxicity warrants caution for concentrated formulations. According to GHS classification, the extract aligns with Category 5 (acute oral toxicity, lowest hazard) and Category 2 (germ cell mutagenicity). These findings underscore the importance of dose management and further long-term genotoxicity studies before translational applications in nutraceutical or biomedical fields. Full article
(This article belongs to the Section Molecular Toxicology)
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18 pages, 10748 KB  
Article
GhTGA2, a Potential Key Regulator of Salt Stress Response: Insights from Genome-Wide Identification of TGA Family Genes Across Ten Cotton Species
by Lu Meng, Jiliang Fan, Shandang Shi, Faren Zhu, Ganggang Zhang, Junwei Wang, Zihan Li, Fei Wang and Hongbin Li
Genes 2025, 16(10), 1143; https://doi.org/10.3390/genes16101143 - 26 Sep 2025
Abstract
Background: The TGACG-BINDING FACTORS (TGA) gene family, a key subgroup of bZIP transcription factors, mediates plant stress responses and developmental processes by binding to the as-1 cis-element in target gene promoters to regulate transcriptional activation or repression. Despite its functional significance, systematic [...] Read more.
Background: The TGACG-BINDING FACTORS (TGA) gene family, a key subgroup of bZIP transcription factors, mediates plant stress responses and developmental processes by binding to the as-1 cis-element in target gene promoters to regulate transcriptional activation or repression. Despite its functional significance, systematic characterization of TGA genes in cotton (Gossypium spp.) remains insufficient. Methods: In this study, we performed a comprehensive genome-wide identification and phylogenetic analysis of TGA members across 10 Gossypium species and verified the functions of candidate genes using VIGS technology. Results: A total of 74 TGA homologous genes with conserved DOG1 and bZIP domains were identified. Evolutionary analysis revealed that the cotton TGA gene family can be classified into five distinct branches, suggesting functional diversification. Functional prediction analyses indicated these genes in cotton growth regulation and stress adaptation, potentially through hormone-mediated signaling pathways. Expression profiling demonstrated both tissue-specific expression patterns and salt-stress responsiveness in Gossypium hirsutum TGA genes, and GhTGA2 exhibited the most significant up-regulated expression under salt stress. Virus-induced gene silencing (VIGS)-mediated GhTGA2 silencing significantly reduced the salt tolerance in cotton. Conclusions: The TGA gene family is involved in regulating cotton growth, development, and stress responses, and plays a critical role in mediating salt stress tolerance in cotton. Our results provide mechanistic insights into cotton stress adaptation and establish a valuable genetic resource for developing elite salt-tolerant cotton cultivars, with direct implications for sustainable cotton production. Full article
(This article belongs to the Special Issue Molecular Genetics of Stress Response in Crops)
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Article
Involvement of Ethylene in Adventitious Root Formation of Red-Stalked Rhubarb In Vitro
by Agnieszka Wojtania, Piotr Waligórski and Monika Markiewicz
Int. J. Mol. Sci. 2025, 26(19), 9429; https://doi.org/10.3390/ijms26199429 - 26 Sep 2025
Abstract
Irregular rooting in vitro is a major problem in the micropropagation of culinary rhubarb (Rheum rhaponticum), a vegetable crop rich in bioactive compounds. To date, little is known about the factors and mechanisms underlying adventitious root (AR) formation in rhubarb under [...] Read more.
Irregular rooting in vitro is a major problem in the micropropagation of culinary rhubarb (Rheum rhaponticum), a vegetable crop rich in bioactive compounds. To date, little is known about the factors and mechanisms underlying adventitious root (AR) formation in rhubarb under in vitro conditions. Here, we studied the effects of indole-3-butyric acid (IBA) and its interaction with ethylene (ET) on AR development in rhubarb ‘Raspberry’ selection. To evaluate the ET-effect, we applied a precursor of ET biosynthesis—1 aminocyclopropane-1-carboxylic acid (ACC); an inhibitor of ET synthesis—aminoethoxyvinylglycine (AVG); and an inhibitor of ET action—silver nitrate (AgNO3). The best results (96.9% rooting frequency, 12.7 roots/shoot) were obtained after adding ACC to the IBA-containing medium. The positive effect of ET was linked to decreased levels of cytokinin and auxins in the rhubarb shoot bases at the initiation and expression stages of rooting. Moreover, the enhanced expression levels of genes involved in auxin signalling and homeostasis (IAA17, GH3.1) and ABA catabolism (CYP707A1) were observed. The blocking of ethylene synthesis significantly increased JA production, and the rooting frequency decreased to 29.8%. The presence of AgNO3 in the auxin medium resulted in a significant reduction in root number, which was consistent with the enhanced levels of ABA and the expression of genes related to ABA biosynthesis and signalling (PP2C49 and CBF4), as well as ET synthesis (ACO5). Full article
(This article belongs to the Special Issue Plant Hormone Signaling)
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