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26 pages, 603 KB  
Article
The D’Alembert Inevitability Theorem
by Jonathan Washburn, Milan Zlatanović and Elshad Allahyarov
Mathematics 2026, 14(8), 1386; https://doi.org/10.3390/math14081386 - 20 Apr 2026
Abstract
We study functions satisfying the composition law F(xy)+F(x/y)=P(F(x),F(y)) with a symmetric polynomial combiner P. We prove that symmetry [...] Read more.
We study functions satisfying the composition law F(xy)+F(x/y)=P(F(x),F(y)) with a symmetric polynomial combiner P. We prove that symmetry together with a quadratic degree bound on P forces a composition law of d’Alembert type. We establish a degree mismatch exclusion criterion showing that symmetric polynomial combiners with degP(u,v)3 do not admit nonconstant continuous solutions, provided the leading term does not cancel (Theorem 1). For continuous nonconstant functions F:R>0R with F(1)=0 satisfying the composition law with a symmetric polynomial P of degree at most two, the combiner is necessarily of the form P(u,v)=2u+2v+cuv, cR (Theorem 3). The equation reduces in logarithmic coordinates to the classical d’Alembert functional equation. For c0, one obtains hyperbolic or trigonometric branches, while c=0 yields the squared-logarithm family. Under the cost-function assumptions F0 and convexity, only the hyperbolic branch with c>0 remains. A unit log-curvature calibration selects the canonical value c=2, which yields the canonical reciprocal cost F(x)=12(x+x1)1. For c0, the result extends to R>0n: every solution depends only on a single linear combination of coordinate logarithms; for c=0, the solution is a general quadratic form i,jaijlnxilnxj. In either case, nontrivial coordinate-wise separable costs are excluded. Full article
(This article belongs to the Section C: Mathematical Analysis)
25 pages, 6172 KB  
Article
Transcriptional and Alternative Splicing Regulation of Autophagy and Vesicle Transport Pathways in Large Yellow Croaker Cells During Megalocytivirus Infection
by Zaiyu Zheng, Hongshu Chi, Xiaodong Liu, Xiuxia Chen, Ying Pan and Hui Gong
Animals 2026, 16(8), 1259; https://doi.org/10.3390/ani16081259 - 20 Apr 2026
Abstract
Infection of the large yellow croaker (Larimichthys crocea) embryo cell line YCE1 with megalocytivirus strain FD201807 leads to accumulation of capsid-deficient viral intermediates within intracellular vesicles at 48 h post-infection (a phenotype associated with non-lytic egress), which coincides with the initial [...] Read more.
Infection of the large yellow croaker (Larimichthys crocea) embryo cell line YCE1 with megalocytivirus strain FD201807 leads to accumulation of capsid-deficient viral intermediates within intracellular vesicles at 48 h post-infection (a phenotype associated with non-lytic egress), which coincides with the initial peak of viral genomic copies. To characterize the host molecular response during this critical stage, we performed time-course RNA sequencing at 24, 48, 96, and 144 hpi. Integrated analysis identified 6661 differentially expressed genes (DEGs) and 1138 differential alternative splicing (DAS) events affecting 892 genes, with DAS event abundance peaking at 48 h. DAS genes in autophagy and Golgi vesicle transport pathways, both integral to animal innate immunity, were significantly enriched exclusively at this timepoint, featuring novel mutually exclusive exon (MXE) isoforms in gopc (Golgi-associated PDZ and coiled-coil motif containing) and rint1 (RAD50 interactor 1). Weighted gene co-expression network analysis (WGCNA) of DEGs identified mapk9 (mitogen-activated protein kinase 9) and map1lc3a (microtubule-associated protein 1 light chain 3 alpha) as hub genes within modules enriched for autophagy-related functions. Separate co-expression analysis of DAS genes revealed rnf5, rimoc1, and golga4 as hub genes, with gopc exhibiting only a single linkage to rnf5. These findings implied concurrent transcriptional and virus-induced host splicing regulation of vesicle-associated innate defense pathways and suggest that splicing-derived features may serve as potential candidates for diagnostics or prevention against megalocytivirus disease in L. crocea. Full article
(This article belongs to the Special Issue Innate Host Defence Mechanisms of Aquatic Animals)
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19 pages, 3869 KB  
Article
Integrative Analysis of Volatile Flavor Compounds and Transcriptome Reveals Underlying Mechanisms Linked to Fatty Acid Content in Dabieshan Cattle
by Liu Zhang, Qian Li, Hai Jin, Shuanping Zhao, Huibin Zhang, Xinyi Du, Qinggang Li and Lei Xu
Foods 2026, 15(8), 1423; https://doi.org/10.3390/foods15081423 - 19 Apr 2026
Viewed by 148
Abstract
To investigate the associations between genes involved in fatty acid composition and volatile flavor compounds (VOCs), Dabieshan (DBS) cattle were selected and stratified into high (H: 0.018–0.024 g) and low (L: 0.007–0.012 g) groups according to the fatty acid content in the longissimus [...] Read more.
To investigate the associations between genes involved in fatty acid composition and volatile flavor compounds (VOCs), Dabieshan (DBS) cattle were selected and stratified into high (H: 0.018–0.024 g) and low (L: 0.007–0.012 g) groups according to the fatty acid content in the longissimus dorsi (LD). Integrated analysis using two-dimensional gas chromatography–time-of-flight mass spectrometry (GC×GC-TOF-MS) and transcriptomics systematically revealed differences in VOCs and gene expression profiles, along with their associations with fatty acid composition. The relative contents of aldehydes, esters, and hydrocarbons were significantly higher in the group H, whereas the group L exhibited elevated levels of alcohols, acids, and heterocyclic compounds. Among 54 differentially abundant VOCs identified, (E)-2-Nonenal (ROAV = 100) was established as the key flavor contributor. Transcriptomic analysis identified 678 differentially expressed genes (DEGs), with eight candidate genes implicated in fatty acid composition pinpointed through GO and KEGG enrichment analyses. Further correlation analysis showed that the expression levels of SGPL1, KLF15 and SLC27A6 were significantly correlated with the contents of polyunsaturated fatty acids (C22:5n-3, C18:3n-3, C18:2n-6, C18:1n-9c). There was also a significant correlation between the above fatty acids and characteristic flavor compounds including 3-Hexanone, (E)-2-Nonenal, (E,E)-2,4-Octadienal and Butanal. This study suggested potential links among fatty acid composition, key genes and characteristic flavor compounds in Dabieshan cattle, providing new insights into the genetic improvement of flavor quality of local cattle breeds. Full article
(This article belongs to the Special Issue Advanced Understanding of Meat Matrix-Flavor Relationships)
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27 pages, 2780 KB  
Article
Identification and Integration of LRG1-Induced Differentially Expressed Gene (DEG) Hub Profiles in Breast Cancer Cells
by Federico Osorio-Antonio, Daniela Michel Diaz-González, Gabriela Elizabeth Campos-Viguri, José Manuel Sánchez-López, José Luis Cortez-Sánchez, Francisco Castelán, Jesús Ramses Chávez-Rios, Paola Maycotte-González, Paulina Cortés-Hernández, Oscar Peralta-Zaragoza and Elizabeth Bautista-Rodríguez
Int. J. Mol. Sci. 2026, 27(8), 3613; https://doi.org/10.3390/ijms27083613 - 18 Apr 2026
Viewed by 209
Abstract
Breast carcinoma is a major cause of cancer-related mortality among women worldwide. Identifying novel molecular targets remains essential, particularly for aggressive triple-negative breast cancer (TNBC). Leucine-rich alpha-2-glycoprotein 1 (LRG1) has been linked to tumor progression and angiogenesis, but its molecular mechanisms in breast [...] Read more.
Breast carcinoma is a major cause of cancer-related mortality among women worldwide. Identifying novel molecular targets remains essential, particularly for aggressive triple-negative breast cancer (TNBC). Leucine-rich alpha-2-glycoprotein 1 (LRG1) has been linked to tumor progression and angiogenesis, but its molecular mechanisms in breast cancer are poorly defined. We evaluated the effects of recombinant human LRG1 (rhLRG1) on cell viability and migration in MDA-MB-231 TNBC cells and performed transcriptomic profiling followed by functional enrichment analyses using GenArise, Cytoscape, and R-based tools. RhLRG1 treatment significantly increased cell viability and migration. Transcriptomic analysis revealed activation of key oncogenic cascades, including the PI3K/AKT, MAPK, and RAS signaling pathways. Hub-gene analysis identified upregulated genes involved in proliferation (NRAS, STAT5B, IGF2), angiogenesis (PGF, ANGPT2), and apoptosis (CASP8, BAD), whereas downregulated genes were associated with apoptotic resistance (BCL2, MCL1) and adhesion (LAMB1, ITGB4). Functional enrichment highlighted LRG1’s role in the bioinformatic analysis of differentially expressed genes that were obtained from microarray assays. LRG1 remodels the tumor microenvironment by promoting proliferation, angiogenesis, and apoptotic sensitivity while repressing resistance-related genes. These findings position LRG1 as a potential diagnostic biomarker and therapeutic target for advanced breast carcinoma. Full article
(This article belongs to the Section Molecular Oncology)
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20 pages, 2511 KB  
Article
Integrated Physio-Biochemistry and Transcriptome Analysis Reveals the Mechanism of 24-Epibrassinolide in Alleviating Cadmium Stress in Watermelon (Citrullus lanatus L.)
by Jingqiu Xu, Yuanyuan Chen, Mengmeng Liu and Haidong Ding
Biology 2026, 15(8), 638; https://doi.org/10.3390/biology15080638 - 18 Apr 2026
Viewed by 143
Abstract
Cadmium (Cd) contamination is widely recognized as a major risk factor affecting the security and quality of crop production. Watermelon (Citrullus lanatus) is a globally cultivated fruit that is susceptible to Cd stress. 24-Epibrassinolide (EBR), an active brassinosteroid, is essential for [...] Read more.
Cadmium (Cd) contamination is widely recognized as a major risk factor affecting the security and quality of crop production. Watermelon (Citrullus lanatus) is a globally cultivated fruit that is susceptible to Cd stress. 24-Epibrassinolide (EBR), an active brassinosteroid, is essential for plant growth and abiotic stress responses. However, its protective role in watermelon under Cd stress remains unclear. This study elucidates the physiological and molecular processes underlying EBR-mediated alleviation of Cd toxicity in watermelon seedlings. The results showed that exogenous EBR application effectively mitigated Cd-induced growth inhibition through decreased Cd deposition, reduced the accumulation of reactive oxygen species (ROS), lowered membrane lipid peroxidation, and increased antioxidant capacity in watermelon leaves under Cd treatment. Transcriptome (RNA-Seq) analysis revealed that EBR triggered substantial reprogramming of gene expression patterns, identifying 530 differentially expressed genes (DEGs) in Cd + EBR co-treatment compared with Cd treatment alone, including 204 down-regulated genes and 326 up-regulated genes. These DEGs are vital for controlling several physiological processes, including phenylpropane metabolism, phenylpropanoid biosynthesis, endoplasmic reticulum’s protein production, cell wall organization, and others. Further physiological assays confirmed that EBR increased the activities of PAL and 4CL, the core enzymes driving phenylpropanoid biosynthesis, leading to a significant accumulation of total phenols and flavonoids. Together, the above results give concrete proof of the powerful functions of 24-EBR, acting as an enhancer of plant performance under Cd stress by enhancing the antioxidant system and by activating the phenylpropanoid pathway and its derived metabolic networks. Full article
(This article belongs to the Section Plant Science)
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21 pages, 3822 KB  
Article
Ammonia Exposure Elevated 5-HT Expression, Reprogrammed Transcriptome and Microbiota Community in Yellow Catfish (Pelteobagrus fulvidraco) Gill During Early Ontogeny
by Yuqing Jian, Kexin Xiong, Jiahong Zou, Xinyue Du, Shihao Liu, Yaoqiang Yue, Jian Gao, Wenjie Guo and Qingchao Wang
Microorganisms 2026, 14(4), 912; https://doi.org/10.3390/microorganisms14040912 - 17 Apr 2026
Viewed by 126
Abstract
The accumulated ammonia within the recirculating aquaculture systems threaten fish health, while little is known about the influences during early fish ontogeny. Using larval and juvenile yellow catfish (Pelteobagrus fulvidraco) as a model, a comprehensive experiment exposing fish to varying total [...] Read more.
The accumulated ammonia within the recirculating aquaculture systems threaten fish health, while little is known about the influences during early fish ontogeny. Using larval and juvenile yellow catfish (Pelteobagrus fulvidraco) as a model, a comprehensive experiment exposing fish to varying total ammonia nitrogen concentrations (0, 10, 20 mg/L for larvae; 0, 25, 125 mg/L for juveniles) was conducted to evaluate the effects on gill transcriptome and microbiota along with the serotonergic regulation. First, the serotonin (5-HT) signal, which controls oxygen chemoreception and ventilation, was mainly detected in the surface of the body of the larvae, and then shifted to gill filaments of juveniles, showing a transition from cutaneous to branchial respiration. Both larval and juvenile yellow catfish exhibited reduced survival, damaged gill structure, and elevated 5-HT expression after ammonia exposure, as well as upregulated tph1b, slc6a4b, scgn and lama5 expression with the increased ammonia concentration, indicating the effects on respiratory function via serotonergic regulation. Further transcriptome analysis was conducted in juveniles to identify the differentially expressed genes (DEGs) and thus, to illustrate more detailed responses after ammonia exposure; KEGG enrichment analysis of DEGs indicated the coping strategy shifted from metabolic buffering to metabolic elimination via glutamine synthesis with the increased ammonia level. The qRT-PCR experiment also identified the increased expression of genes involved in the urea cycle—such as ass1, asl and glula—with the increased ammonia level. Considering the potential contributary role of microbiome to gill health, 16S sequencing was conducted on the gill in the control and the 125 mg/L ammonia-exposed group. Ammonia exposure at 125 mg/L induced significant variation in Simpson index and a marked decline in β diversity. Notably, the abundance of opportunistic pathogens such as Pseudomonadota increased, while the abundance of Deinococcota and Deinococcus—which were renowned for exceptional stress resistance capacity—decreased after ammonia exposure. Thus ammonia exposure disrupts the transcriptomic and microecological balance within gill mucosa, which may elevate the risk of pathogenic infection. Overall, our study provided the first evidence of serotonergic regulation on early fish respiration during ammonia exposure, and also offered new theoretical insights into the involvement of microorganisms in ammonia toxicity. Full article
(This article belongs to the Special Issue Microbiome in Fish and Their Living Environment, Second Edition)
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18 pages, 2154 KB  
Article
Decoding Prognostic Signatures in Brain Metastatic Non-Small-Cell Lung Cancer via Integrated Multi-Omics and Network Analysis
by Prithvi Singh, Ravins Dohare, Tarique Sarwar, Hajed Obaid A. Alharbi and Arshad Husain Rahmani
Int. J. Mol. Sci. 2026, 27(8), 3598; https://doi.org/10.3390/ijms27083598 - 17 Apr 2026
Viewed by 149
Abstract
Non-small-cell lung cancer (NSCLC) constitutes approximately all lung cancers (LCs), and metastasis remains a major challenge in its treatment, thus necessitating the detection of novel molecular players involved in this process. In this study, we performed a comprehensive analysis of microarray and RNA-seq [...] Read more.
Non-small-cell lung cancer (NSCLC) constitutes approximately all lung cancers (LCs), and metastasis remains a major challenge in its treatment, thus necessitating the detection of novel molecular players involved in this process. In this study, we performed a comprehensive analysis of microarray and RNA-seq cohorts extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) and associated them with metastasis-related genes involved in brain metastasis (BM) in NSCLC. We thus identified differentially expressed metastatic genes (DEMGs) and constructed a protein–protein interaction network (PPIN) using these DEMGs. These DEMGs were further analyzed for associations with patient age, gender, and tumor stage, and the significant impact of specific genes on overall survival (OS) was assessed to determine the prognostic significance of the identified targets. We finally constructed a three-node microRNA (miRNA) feed-forward loop (FFL) involving miR-23b-3p, CD44, and five transcription factors (TFs) [EOMES, FOS, FOSL1, GLIS3, TP63] specific to NSCLC metastasis. Further mutational analysis of these FFL elements revealed that all were altered in the patient samples analyzed. Thus, our study identified potential genomic drivers that may play crucial roles in NSCLC BM. Overall, it provides valuable insights for the discovery of novel therapeutic targets in the management of NSCLC metastasis. However, further in vitro and in vivo experimentations are needed to justify the prognostic role of NSCLC biomarkers in BM pathogenesis. Full article
(This article belongs to the Special Issue Advances in Multi-Omics in Cancer: Second Edition)
16 pages, 21019 KB  
Article
Identification, Bioinformatics, and Expression Analysis of JAZ Gene Family in Flax (Linum usitatissimum L.)
by Liuxi Yi, Ying Sun, Yu Zhou, Yingnan Mu, Wenyu Han, Yuheng Dong, Huiqing Lan, Jianping Zhang and Yongsheng Chen
Int. J. Mol. Sci. 2026, 27(8), 3594; https://doi.org/10.3390/ijms27083594 - 17 Apr 2026
Viewed by 194
Abstract
Jasmonate ZIM-domain (JAZ) proteins, as core negative regulatory factors of the jasmonic acid (JA) signaling pathway, play a key role in the growth and development of plants and the response to biotic and abiotic stress. In this study, 11 flax JAZ members were [...] Read more.
Jasmonate ZIM-domain (JAZ) proteins, as core negative regulatory factors of the jasmonic acid (JA) signaling pathway, play a key role in the growth and development of plants and the response to biotic and abiotic stress. In this study, 11 flax JAZ members were identified, all of which contain a ZIM domain and a Jas domain. LuJAZs comprise 3–16 exons, encoding 187–808 amino acids (aa) with molecular weights ranging from 20.24 to 88.76 kDa and isoelectric points (PI) of 5.68–9.77. They are all hydrophilic proteins located in the nucleus. These 11 LuJAZ genes are divided into five subfamilies and are unevenly distributed on chromosomes. Transcriptome and qRT-PCR analyses revealed that six LuJAZ genes, including LUSG00004384, LUSG00030782, LUSG00016742, LUSG00004390, LUSG00010997, and LUSG00029783, are significantly induced by JA. The protein–protein interaction (PPI) prediction and analysis of differential expression genes (DEGs) suggest that the MYC2 gene (LUSG00028070) may play a role in the JA-induced response. This study provides a theoretical basis for further exploring the function of the JAZ family in flax. Full article
(This article belongs to the Section Molecular Plant Sciences)
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24 pages, 6684 KB  
Article
Molecular Regulation of Fruit Quality Traits in Citrus: RNA-Seq-Based Meta-Analysis
by Prasanth Tej Kumar Jagannadham, Anbazhagan Thirugnanavel, Tejaswini S. Parteki, Dedoas T. Meshram, Anoop Kumar Srivastava and Vasileios Ziogas
Horticulturae 2026, 12(4), 492; https://doi.org/10.3390/horticulturae12040492 - 17 Apr 2026
Viewed by 313
Abstract
Citrus genomes as storehouses of genetic information of immense commercial utility remain untapped for the improvement of fruit quality traits and other production-related stresses. With the rapid expansion of transcriptomic datasets, integrative meta-analysis has further aided in uncovering interspecies molecular mechanisms associated with [...] Read more.
Citrus genomes as storehouses of genetic information of immense commercial utility remain untapped for the improvement of fruit quality traits and other production-related stresses. With the rapid expansion of transcriptomic datasets, integrative meta-analysis has further aided in uncovering interspecies molecular mechanisms associated with fruit quality development. In this study, we performed a cross-project RNA-Seq meta-analysis, integrating multiple publicly available BioProjects encompassing diverse citrus species, viz., Citrus sinensis, C. reticulata, C. maxima, C. clementina, C. japonica, and C. papeda, known to dominate the morphogenetic evolution of the citrus industry. High-throughput RNA-Seq data were processed using various bioinformatics tools. A total of 15 interspecies comparisons identified 676 unique DEGs, enriched in pathways related to secondary juice yield and processing quality traits. We also established that domestication aided in metabolism, oxidative stress responses, phenylpropanoid and flavonoid biosynthesis, and hormone-mediated signaling. Multivariate analyses (PCA and heatmap visualization) highlighted distinct yet overlapping expression patterns across these citrus species. By combining differential expression, co-expression network analysis and QTL-GWAS integration, we identified 19 high-confidence candidate genes responsible for transcriptomic variation associated with measurable fruit quality traits. Genes such as LOC102612823 and LOC102607495, which co-localized with seed number QTLs on chromosome 1, represented strong candidates regulating reproductive development and seed formation, the traits that directly influence fruit texture and market acceptability. Genes linked to juice content QTLs, including LOC102611137 and LOC102612553 on chromosome 5, suggested their roles in metabolic regulations behind juice accumulation. These loci provided definitive breeding clues for enhancing the reshaping of citrus fruit transcriptomes while retaining key ancestral regulatory components. Full article
(This article belongs to the Special Issue Innovative Breeding Technology for Citrus)
16 pages, 1742 KB  
Article
Integrated Insights into Drought Tolerance Mechanism of the Autotetraploid from Gossypium herbaceum by Transcriptome and Physiological Analyses
by Lili Feng, Lexiang Wang, Jiamin Li, Xianglong Li, Erhua Rong and Yuxiang Wu
Genes 2026, 17(4), 470; https://doi.org/10.3390/genes17040470 - 17 Apr 2026
Viewed by 181
Abstract
Background: Information on the autopolyploid of Gossypium herbaceum remains limited until now. Previously, the autotetraploid of G. herbaceum was successfully generated via colchicine-induced chromosome doubling from the diploid cultivar ‘Hongxing’ in our lab. Methods: To investigate the drought stress response mechanism of this [...] Read more.
Background: Information on the autopolyploid of Gossypium herbaceum remains limited until now. Previously, the autotetraploid of G. herbaceum was successfully generated via colchicine-induced chromosome doubling from the diploid cultivar ‘Hongxing’ in our lab. Methods: To investigate the drought stress response mechanism of this tetraploid, the autotetraploid S4 was used as the experimental material. The plants were subjected to drought stress during the flowering stage, followed by measurements of physiological and biochemical indicators and transcriptomic sequencing analysis. Results: Under drought stress, MDA content increased, and cell membranes sustained oxidative damage. Photosynthetic parameters, such as net photosynthetic rate (Pn), were significantly suppressed, while the activity of osmotic regulators and key antioxidant enzymes increased significantly. After rehydration, all of the above physiological indicators showed varying degrees of recovery. Transcriptome analysis revealed that, when comparing the treatment group with the control group, a total of 5530 differentially expressed genes (DEGs) were identified, with 2714 up-regulated and 2816 down-regulated. Furthermore, this study investigated the drought resistance mechanism involving the interaction between the MAPK signaling pathway and other metabolic pathways in the autotetraploid. Nine drought-resistant genes, including MAPK3, bHLH47, GaRbohD, RIBA1, PIP1-3, RCA1, RbohD, CYP707A and HSP70, were selected and analyzed using real-time quantitative PCR; the results were generally consistent with the transcriptomic data. Conclusions: These findings substantially enhance our understanding of the molecular mechanisms underlying drought responses in autotetraploids. This novel autotetraploid genotype expands the available cotton germplasm resources and is expected to hold significant value for research on polyploidy evolution. Full article
(This article belongs to the Special Issue Abiotic Stress in Crop: Molecular Genetics and Genomics)
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15 pages, 5944 KB  
Article
Transcriptome Sequencing and Differential Analysis of Testes in One- and Two-Year-Old Kazakh Horses
by Yi Su, Liuxiang Wen, Jiaqi Jiang, Mingyue Wen, Yaqi Zeng, Jun Meng, Jianwen Wang, Wanlu Ren and Xinkui Yao
Animals 2026, 16(8), 1220; https://doi.org/10.3390/ani16081220 - 16 Apr 2026
Viewed by 115
Abstract
This study systematically elucidated the developmental characteristics and molecular regulatory mechanisms of the testis during the critical period of sexual maturation in Kazakh horses by combining histological observation of one- and two-year-old testicular tissues with transcriptomic sequencing. In the testes of one-year-old horses, [...] Read more.
This study systematically elucidated the developmental characteristics and molecular regulatory mechanisms of the testis during the critical period of sexual maturation in Kazakh horses by combining histological observation of one- and two-year-old testicular tissues with transcriptomic sequencing. In the testes of one-year-old horses, no obvious lumen was observed, and the interior is mainly comprising supporting cells and spermatogonia on the basement membrane; in contrast, in the testes of two-year-old horses, the tubular lumen was complete with spermatogonia, spermatocytes, and spermatozoa, indicating that spermatogenic function had approached maturity. Transcriptome profiling identified 979 differentially expressed genes (DEGs), with 209 up-regulated genes, including CYP11A1 and CATSPER2, and 770 down-regulated genes, including CD9. Gene Ontology (GO) annotation indicated primary enrichment of DEGs in biological processes related to multicellular organism development, cell membrane composition, and ion binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed significant enrichment of DEGs in the calcium signaling pathway, cell adhesion molecules, and neuroactive ligand–receptor interaction, among other key pathways. Protein–protein interaction (PPI) network analysis further highlighted core genes, including TNF, CATSPER2, and CDH13. Validation by RT-qPCR confirmed the reliability of the RNA-Seq data. Our findings reveal the dynamics of testicular development in Kazakh horses through histological and molecular analyses, thereby providing a theoretical framework and candidate genes to further elucidate regulatory mechanisms and guide genetic improvement in reproductive traits. Full article
(This article belongs to the Section Animal Reproduction)
21 pages, 4428 KB  
Review
Intron Retention as a Homeostatic State Variable for Drug Response and Recovery: Lessons from Depression for Broader Applications
by Norihiro Okada, Kenshiro Oshima, Akiko Maruko, Akinori Nishi and Yoshinori Kobayashi
Int. J. Mol. Sci. 2026, 27(8), 3539; https://doi.org/10.3390/ijms27083539 - 16 Apr 2026
Viewed by 269
Abstract
Clinically robust molecular biomarkers for depression have remained elusive, despite extensive transcriptomic research. This gap is consequential: depression is prevalent and heterogeneous, yet objective measures to quantify burden, stratify patients, and track recovery remain limited. Here, we review evidence that intron retention (IR) [...] Read more.
Clinically robust molecular biomarkers for depression have remained elusive, despite extensive transcriptomic research. This gap is consequential: depression is prevalent and heterogeneous, yet objective measures to quantify burden, stratify patients, and track recovery remain limited. Here, we review evidence that intron retention (IR) can serve as a homeostatic state variable—and therefore a sensitive biomarker—reporting stress adaptation and recovery at an upstream regulatory layer, often preceding or outperforming differential gene expression (DEG) readouts. Mechanistically, IR enables bidirectional fine-tuning of effective gene output: increased IR (IncIR) can throttle output under overload, whereas decreased IR (DecIR) releases this brake to restore gene output. Because these shifts are reversible and treatment-responsive, IR signatures can function not only as disease markers but also as pharmacodynamic metrics for blood-based monitoring of drug response and recovery. To evaluate the clinical utility of IR, we use depression as a proof of concept and focus on two interventions: (i) the Kampo formula hangekobokuto (HKT), which is associated with IR normalization consistent with reduced peripheral inflammatory load; and (ii) ketamine, where IR patterns measured before ketamine treatment in non-responders are linked to stronger innate-immune/antiviral activity, suggesting a higher inflammatory load that may limit treatment benefit. Finally, we discuss transdiagnostic extensions beyond depression, using early cognitive decline (mild cognitive impairment, MCI) as a stringent, biologically distal test case for blood-based IR/DI readouts and motivating independent cohort replication and longitudinal validation. Full article
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19 pages, 8791 KB  
Article
Single-Cell Analysis Highlights Pivotal Role of Eosinophil–Basophil Mast Cell Progenitor-Related Mechanism in Primary Immune Thrombocytopenia
by Mei Xie, Haimei Deng, Fangjie Liu, Wei Xiao, Xiaojun Xu, Rongli Xie and Tiantian Sun
Int. J. Mol. Sci. 2026, 27(8), 3535; https://doi.org/10.3390/ijms27083535 - 15 Apr 2026
Viewed by 210
Abstract
Immune thrombocytopenia (ITP) is an autoimmune disease. Megakaryocyte dysfunction caused by autoimmune response can lead to thrombocytopenia, and the underlying mechanism is still unclear. Single-cell sequencing analysis revealed the heterogeneity of CD34 + HSPCs in bone marrow between ITP patients and healthy groups. [...] Read more.
Immune thrombocytopenia (ITP) is an autoimmune disease. Megakaryocyte dysfunction caused by autoimmune response can lead to thrombocytopenia, and the underlying mechanism is still unclear. Single-cell sequencing analysis revealed the heterogeneity of CD34 + HSPCs in bone marrow between ITP patients and healthy groups. Pre-B cell population 1 (pre-B1) showed a significantly lower percentage contribution in ITP groups, and the underlying mechanism involves cell cycle-, cell apoptosis- and cell death-related pathways. The number of eosinophil–basophil mast cell progenitors (EBMPs) is significantly increased in ITP patients and the DEGs of the EBMPs in ITP patients were significantly enriched in immune-related pathways. Further, immunofluorescent staining and Western blot assay highlight C-X-C Motif Chemokine Ligand 8 (CXCL8) and Interferon Regulatory Factor 1 (IRF1) expression were significantly increased in the EBMPs of ITP patients. Furthermore, cell–cell communication analysis identified an impaired LGALS9-CD44 axis between EBMP cells and MkP1 cells in ITP patients, suggesting that targeting the LGALS9-CD44 interaction might hold promise as a therapeutic approach for ITP. Our observations indicate that ITP patients exhibit an elevated proportion of EBMP cells alongside a reduced proportion of pre-B1 cells. CXCL8 and IRF1 are potentially associated with EBMP cell dysfunction and the ITP disease process. Furthermore, the diminished LGALS9-CD44 axis between EBMP and MkP1 cells may contribute to ITP progression, suggesting a direction for future therapeutic investigation. Full article
(This article belongs to the Section Molecular Immunology)
18 pages, 21666 KB  
Article
Analysis of Axillary Bud Germination Regulatory Network in Sugarcane Based on Transcriptome and Weighted Gene Co-Expression Network Analysis
by Yanye Li, Ting Yang, Zongtao Yang, Xujuan Li, Xin Lu, Jianming Wu, Jiayong Liu, Fenggang Zan, Yong Zhao, Jun Deng and Xinlong Liu
Plants 2026, 15(8), 1200; https://doi.org/10.3390/plants15081200 - 14 Apr 2026
Viewed by 340
Abstract
Axillary bud germination in sugarcane is a critical agronomic trait that directly determines seedling emergence and tillering capacity; however, its molecular regulatory mechanisms remain poorly understood. In this study, we systematically investigated the hormonal dynamics and transcriptomic profiles of the sugarcane cultivar XTT22 [...] Read more.
Axillary bud germination in sugarcane is a critical agronomic trait that directly determines seedling emergence and tillering capacity; however, its molecular regulatory mechanisms remain poorly understood. In this study, we systematically investigated the hormonal dynamics and transcriptomic profiles of the sugarcane cultivar XTT22 across five developmental stages (from dormancy to the first new leaf stage). Our results revealed that abscisic acid (ABA) content fluctuated during germination, whereas indole-3-acetic acid (IAA) and gibberellin (GA) levels decreased significantly, suggesting their negative regulatory roles. In contrast, cytokinin (CTK) and ethylene (ETH) contents increased at the initiation stage, indicating positive promoting functions. Transcriptome analysis identified 31,513 differentially expressed genes (DEGs), which were significantly enriched in pathways related to hormone signal transduction, starch/sucrose metabolism, and photosynthesis. Weighted gene co-expression network analysis (WGCNA) constructed 12 co-expression modules, among which the antiquewhite4 module (negatively correlated with IAA, GA, and ABA contents) and the darkorange2 module (positively correlated with cytokinin content) were identified as key regulatory modules. From these modules, seven core hub transcription factors (e.g., ScTCP5, ScSCR, and ScSHR1) were screened, and their expression patterns were validated by RT-qPCR. Furthermore, the expression trends of six hormone-related DEGs were highly consistent with the RNA-seq data. Collectively, this study elucidates the hormonal dynamics and gene regulatory networks underlying axillary bud germination in sugarcane, providing candidate gene resources for breeding high-yield varieties with enhanced emergence and tillering capacity. Full article
(This article belongs to the Special Issue Sugarcane Breeding and Biotechnology for Sustainable Agriculture)
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Article
Uncovering Viral Diversity and Host Responses in Saffron via Nanopore RNA Sequencing
by Marzieh Shamshiri, Conchi Sánchez, Jesús Mª Vielba, Nieves Vidal, Masoud Shams-Bakhsh and Saleta Rico
Agronomy 2026, 16(8), 803; https://doi.org/10.3390/agronomy16080803 - 14 Apr 2026
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Abstract
Saffron (Crocus sativus L.) is a high-value crop vulnerable to potyvirus infections threatening its yield and quality. In this study, we combined Oxford Nanopore long-read sequencing with exploratory transcriptomic profiling to characterize the saffron virome and to describe expression profiles associated with [...] Read more.
Saffron (Crocus sativus L.) is a high-value crop vulnerable to potyvirus infections threatening its yield and quality. In this study, we combined Oxford Nanopore long-read sequencing with exploratory transcriptomic profiling to characterize the saffron virome and to describe expression profiles associated with two distinct infection histories: (i) saffron plants experimentally inoculated with cucumber mosaic virus (CMV; Cucumovirus CMV) and turnip mosaic virus (TuMV; Potyvirus rapae) under controlled greenhouse conditions, and (ii) saffron plants naturally infected by diverse viruses. We identified six plant-infecting viral families in both conditions, including Potyviridae, Geminiviridae, Caulimoviridae, Tymoviridae, Aspiviridae, and Partitiviridae. Transcriptomic profiling revealed distinct expression profiles associated with each infection background. Given the limitations of the experimental design, gene expression differences are interpreted descriptively. We describe pathway enrichments associated with antiviral responses. Naturally infected plants exhibited a broad-spectrum, tolerance-based response characterized by the upregulation of photosynthesis-related genes, calcium-mediated signaling components, and stress-responsive transcription factors. In contrast, virus-inoculated plants activated a targeted antiviral program involving RNA silencing, autophagy, ubiquitin-mediated proteolysis, and hormonal regulation. Both GO and KEGG enrichment analyses supported these findings, highlighting photosynthesis and metabolic flexibility in naturally infected plants versus hypersensitive response, RNA surveillance, and lignin biosynthesis in virus-inoculated plants. This work provides a comprehensive view of the saffron virome and offers a hypothesis-generating overview of transcriptional responses associated with natural versus experimental virus infections. These findings advance the understanding of the saffron virome and provide a valuable resource for breeding virus-resistant cultivars. Full article
(This article belongs to the Special Issue New Insights into Plant-Microbe Interaction)
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