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Luteolin is a natural flavonoid compound with multifaceted pharmacological properties, including anti-oxidant, anti-inflammatory, antiviral, and anti-tumor activities. Network pharmacology analysis has been utilized to decipher the underlying mechanisms and multitargets of luteolin against coronavirus disease 2019 (COVID-19). This review aims to provide a systematic and comprehensive summary of luteolin, as a potential novel remedy with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity, as well as its anti-oxidant mechanisms. We systematically delineate the epidemiological profile, genomic architecture, and replicative dynamics of SARS-CoV-2, thereby constructing a multiscale framework to decode its pathogenic mechanisms. Employing a multi-level network pharmacology analytical strategy, we identify 46 core targets through protein interaction network construction, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Molecular investigations reveal luteolin’s dual antiviral mechanisms, including direct targeting of SARS-CoV-2 proteins and host-directed intervention through suppression of angiotensin-converting enzyme 2 receptor engagement/transmembrane protease serine 2-mediated viral priming. The polypharmacological profile of luteolin demonstrates synergistic effects in blocking viral entry, replication, and host inflammatory cascades. This phytochemical repurposing study of luteolin provides a novel mechanistic paradigm for developing multitarget antiviral agents, highlighting the translational value of natural compounds in combating emerging viral variants. Full article

Introduction: Bovine leukemia virus is a single-stranded RNA virus that targets B cell CD5⁺ lymphocytes in cattle. Only a tiny percentage of individuals develop malignant lymphoproliferative disorders, while most remain healthy carriers or experience persistent lymphocytosis. The exact mechanisms leading to lymphoma development are complex and not fully understood. RNA-seq analysis of cows’ peripheral blood leukocytes (PBLs) with and without Bovine leukemia virus (BLV) antibodies was conducted to gain a deeper understanding of molecular events beyond BLV infection. Method: Eighteen samples were selected, and their RNA was sequenced. For gene expression analysis and protein–protein network interactions, three groups were selected, including healthy negative samples (CT, n = 7), asymptomatic carriers (AC, n = 5), and persistent lymphocytosis (PL, n = 6), to provide the differentially expressed gene (DEG) and protein–protein interaction network (PPIN) outputs. Results: Our results demonstrated that in comparison to CT, ACs upregulated TLR7 and transcription activation factors. In the CT vs. PL group, MHC class II, transcription activation factors, and anti-inflammatory cytokines increased, while the acute-phase proteins, antiviral receptors, and inflammatory cytokines decreased. Additionally, antiviral receptors, acute-phase proteins, and inflammatory receptors were downregulated in the PL versus the AC groups. Moreover, PPINs analysis suggested that nuclear receptor corepressor 1 (NCOR1), serine/arginine repetitive matrix 2 (SRRM2), LUC7 like 3 pre-mRNA splicing factor (LUC7L3), TWIST neighbor (TWISTNB), U6 small nuclear RNA and mRNA degradation associated (LSM4), eukaryotic translation elongation factor 2 (EEF2), ubiquitin C (UBC), CD74, and heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNP A2B1) are possible hub gene candidates in the PL group. Conclusions: Our results suggest that innate and cellular immune responses are more loose in severe BLV infectious conditions, while the PPINs revealed that new protein interactions are necessary for oncogenesis. Full article

The tall wheatgrass Thinopyrum ponticum has excellent saline–alkali tolerance and great potential for restoring saline–alkali land to enhance productivity. This study used the Thinopyrum ponticum cv. “Orbit” variety, which is widely planted in saline–alkali pastures, as the material and artificially simulated salt stress using 150 mM NaCl and 150 mM Na₂SO₄, respectively. The growth and physiological indexes of the leaves and roots of seedlings were measured after various treatment durations, and the transcriptomes of untreated and Na₂SO₄-treated leaves and roots were also analyzed after 24 h of treatment. The results showed that salt stress resulted in significant reductions in leaf relative water content in seedlings and inhibited root elongation growth, with Na₂SO₄ treatment producing a greater impact on plant growth than NaCl treatment. Salt stress significantly alters ion transport and distribution in Thinopyrum ponticum, characterized by pronounced Na⁺ accumulation and a concomitant decline in K⁺ uptake. Additionally, to adapt to salt stress, roots enhance their ability to absorb and transport essential cations, such as Ca²⁺, Mg²⁺, Fe³⁺, and Cu²⁺. RNA-Seq analysis identified 1682 and 2816 differentially expressed genes (DEGs) in leaves and roots under Na₂SO₄ stress, respectively, with 210 common DEGs. Enrichment analyses revealed that DEGs were primarily associated with redox homeostasis, ion balance, and signal transduction. Furthermore, transcription regulation analysis indicated the Thinopyrum ponticum can coordinate the activation of NAC/MYB/WRKY transcription factors, SA/ETH hormone signaling, and Ca²⁺ pathways in response to salt stress. In summary, this study systematically reveals for the first time the molecular mechanisms by which Thinopyrum ponticum responds to Na₂SO₄ stress through coordinated regulation of ion transport, transcription factor networks, and hormone-Ca²⁺ signaling pathways. Based on transcriptomic and protein–protein interaction analyses, nine key candidate genes for saline–alkali tolerance were identified, including UGT7472, JMT, T4E14.7, CAX5, CP1, PXG2 NAMT1, BON3, and APX7. These findings provide novel genetic resources and a theoretical foundation for breeding salt–alkali-tolerant crops. Full article

In recent years, research has focused on biomarkers as key tools to predict clinical outcomes and guide therapeutic decisions in Multiple Sclerosis (MS). MicroRNAs (miRs)—small non-coding RNA molecules that regulate gene expression at the post-transcriptional level—have emerged as promising biomarkers in MS due to their accessibility in biological fluids. This study investigates the role of specific serum miRs mainly involved in immune response regulation as potential prognostic biomarkers in MS, focusing on young patients with recent diagnosis. The study had a prospective design, involving a cohort of patients followed in the Hub and Spoke MS network of Verona province. Fifty-one patients (33F) aged 18–40 years with recent MS diagnosis (≤2 years; 45 relapsing-remitting, 6 primary progressive) were consecutively enrolled. At baseline, serum samples were collected for miR analysis alongside clinical-demographic and MRI data, including T2 lesion volume, normalized brain volume (NBV), gray matter volume, white matter volume (WMV) calculated at baseline and annual percentage brain volume change (PBVC) and occurrence of new T2 or gadolinium-enhancing (Gd+) lesions on follow-up scans. Candidate miRs were chosen based on their potential biological role in MS pathogenesis reported in the literature. miRs assays were done using real-time PCR and expressed as a ratio relative to a normalizer (i.e., miR-425-5p). Levels of miR-34a-5p were significantly higher in patients with Gd+ lesions (p < 0.001) and correlated to lower NBV (rho = −0.454, p = 0.001) and WMV (rho = −0.494, p < 0.001). Conversely, miR-140-5p exhibited a protective effect against occurrence of new T2 or Gd+ lesions over time (HR 0.43; IC 95% 0.19–0.99; p = 0.048). Additionally, miR-30b-5p correlated directly with PBVC (adjusted rho = −0.646; p < 0.001). These findings support the potential of serum miR-34a-5p, miR-140-5p, and miR-30b-5p as markers of disease activity and progression in patients with recently diagnosed MS. Full article

Background/Objectives: Cofilin, a key regulator of actin cytoskeleton dynamics, contributes to neuroinflammation, synaptic damage, and blood–brain barrier disruption in ischemic stroke. Despite its established role in stroke pathology, cofilin remains largely untargeted by existing therapeutics. This study aimed to identify potential cofilin-binding molecules by repurposing LIMK1 inhibitors through an integrated computational strategy. Methods: A cheminformatics pipeline combined QSAR modeling with four molecular fingerprint sets and multiple machine learning algorithms. The best-performing QSAR model (substructure–Random Forest) achieved R²_train = 0.8747 and R²_test = 0.8078, supporting the reliability of compound prioritization. Feature importance was assessed through SHAP analysis. Top candidates were subjected to molecular docking against cofilin, followed by 300 ns molecular dynamics simulations, MM-GBSA binding energy calculations, principal component analysis (PCA), and dynamic cross-correlation matrix (DCCM) analyses. Network pharmacology identified overlapping targets between selected compounds and stroke-related genes. Results: Three compounds, CHEMBL3613624, ZINC000653853876, and Gandotinib, were prioritized based on QSAR performance, binding affinity (−6.68, −6.25, and −5.61 Kcal/mol, respectively), and structural relevance. Docking studies confirmed key interactions with Asp98 and His133 on cofilin. Molecular dynamics simulations supported the stability of these interactions, with Gandotinib showing the highest conformational stability, and ZINC000653853876 exhibiting the most favorable energetic profile. Network pharmacology analysis revealed eight intersecting targets, including MAPK1, PRKCB, HDAC1, and serotonin receptors, associated with neuroinflammatory and vascular pathways in strokes. Conclusions: This study presents a rational, integrative repurposing framework for identifying cofilin-targeting compounds with potential therapeutic relevance in ischemic stroke. The selected candidates warrant further experimental validation. Full article

MicroRNAs (miRNAs) play a critical role in gene regulation in plants. Several members of the pentatricopeptide repeat (PPR) family have been identified as predicted targets of Ahyp-miR0005, a miRNA specific to amaranth. PPR proteins are essential for mitochondrial and chloroplast biogenesis, as well as plastid-to-nucleus communication, processes fundamental for retrograde signaling between the plastid and nucleus (RSBPN). In this study, we identified the target of Ahyp-miR0005 and its association with the PPR protein family across Amaranthus hypochondriacus, Arabidopsis thaliana, Nicotiana tabacum, and Solanum lycopersicum. Cleavage inhibition by Ahyp-miR0005 was predicted, and the distribution of miRNA binding sites per target gene was analyzed, including their localization within coding PPR domains. Among the main Ahyp-miR0005 target genes, we identified GUN-1, ABO5, and MORF1. Interaction network analysis revealed that different target genes are co-expressed in response to the same stimulus. Gene expression profiling with the Arabidopsis eFP Browser revealed substantial transcriptional changes in predicted targets under six abiotic stress conditions. We further show that abiotic stresses alter the expression of Ahyp-miR0005 amaranth target genes. We anticipate that the expression of Ahyp-miR0005 in non-amaranth plants could replicate the reorganization and coordination of gene expression through RSBPN, thereby improving plant tolerance to various abiotic stresses. Full article

Local scour around bridge piers is one of the primary causes of structural failure in bridges. Therefore, this study focuses on addressing the estimation of maximum scour depth (d_sm), which is essential for safe and resilient bridge design. Many studies in the last eight decades have included metadata collection and developed around 80 empirical formulas using various scour-affecting parameters of different ranges. To date, a total of 33 formulas have been comparatively analyzed and ranked based on their predictive accuracy. In this study, novel formulas using semi-empirical methods and gene expression programming (GEP) have been developed alongside an artificial neural network (ANN) model to accurately estimate d_sm using 768 observed data points collected from published work, along with eight newly conducted experimental data points in the laboratory. These new formulas/models are systematically compared with 74 empirical literature formulas for their predictive capability. The influential parameters for predicting d_sm are flow intensity, flow shallowness, sediment gradation, sediment coarseness, time, constriction ratio, and Froude number. Performances of the formulas are compared using different statistical metrics such as the coefficient of determination, Nash–Sutcliffe efficiency, mean bias error, and root-mean-squared error. The Gauss–Newton method is employed to solve the nonlinear least-squares problem to develop the semi-empirical formula that outperforms the literature formulas, except the formula from GEP, in terms of statistical performance metrics. However, the feed-forward ANN model outperformed the semi-empirical model during testing and validation phases, respectively, with higher CD (0.790 vs. 0.756), NSE (0.783 vs. 0.750), lower RMSE (0.289 vs. 0.301), and greater prediction accuracy (64.655% vs. 61.935%), providing approximately 15–18% greater accuracy with minimal errors and narrower uncertainty bands. Using user-friendly tools and a strong semi-empirical model, which requires no coding skills, can assist designers and engineers in making accurate predictions in practical bridge design and safety planning. Full article

A complex and gradual process, the epithelial–mesenchymal transition (EMT) occurs both during embryonic development and tumor progression. Cells undergo a transition from an epithelial to a mesenchymal state throughout this process. More and more evidence points to EMT as a cause of increased metastatic spread of prostate cancer (PCa), along with stemness enhancement and therapy resistance. Here, we used bioinformatic methods to analyze gene expression microarray data, single-cell RNA sequencing, oncogenes, and tumor suppressor genes (TSGs) in order to reconstruct the network of differentially expressed genes (DEGs) involved in the epithelial–mesenchymal transition with PCa. No prior study has documented this sort of analysis. We next validated our results using data from the Cancer Genome Atlas (TCGA), which included microarray and single-cell RNA sequencing. Potentially useful in PCa diagnosis and treatment are extracellular matrix in epithelial–mesenchymal transition genes, including ITGBL1, DSC3, COL4A6, ANGPT1, ARMCX1, MICAL2, and EPHA5. In this study, we aimed to shed light on the molecular characteristics and pathways of DEGs in PCa, as well as to identify possible biomarkers that are important in the development and advancement of this cancer. These insights have important implications for understanding prostate cancer progression and for the development of therapeutic strategies targeting ECM-mediated pathways. Full article

End-use quality is a crucial aspect of wheat quality, influencing the type and quality of the produced food products. It is mostly determined by the content and characteristics of the protein as well as the starch in the grain. Being a staple food, wheat provides more than 30% of the total calories and proteins in human diets globally. Wheat grain consists of a protein network, called gluten, which provides wheat doughs with their unique viscoelastic properties. The genetic improvement of end-use quality traits is indispensable to meet the requirements of grain markets, millers, and bakers. Thus, modern approaches such as proteomics and genomics are important to precisely identify alleles, genes, as well as their functions in improving end-use quality. End-use quality is mainly regulated by grain protein content, grain hardness and starch synthase genes, as well as gluten proteins, which can be exploited to improve the quality of wheat for the production of desired wheat cultivars. The aim of this review is to highlight the progress, challenges, and opportunities in breeding for end-use quality in wheat. The paper outlines the following key aspects: (1) challenges associated with breeding for end-use quality and (2) opportunities such as genomic selection, marker-assisted selection (MAS), and genetic variation in landraces and wild relatives for end-use quality improvement and the genes regulating end-use quality. Lastly, the paper discusses the prospects for future quality improvement in wheat. The review provides a comprehensive insight into the effects of genes on regulating end-use quality and serves as baseline information for wheat breeders to guide the development and deployment of wheat cultivars for future quality improvement. Full article

Objectives: Alpinia japonica (A. japonica) is traditionally used for digestive disorders, but its hypolipidemic mechanisms remain unclear. This study investigated the lipid-lowering effects of its fruit (SJGS), rhizome (SJGJ), and leaf (SJY) extracts, exploring their bioactive constituents and organ-specific mechanisms. Methods: Sprague Dawley rats (n = 8/group) fed a high-fat diet received SJGS, SJGJ, or SJY (200 mg/kg/day) for 4 weeks. Serum lipids (TC, TG), liver enzymes (AST, ALT), and intestinal barrier markers (DAO) were measured. Gut microbiota (16S rDNA sequencing), hepatic histopathology, and ileal tight junction proteins were analyzed. Transcriptomics and qPCR assessed ileal gene expression. LC-MS identified chemical constituents, while network pharmacology predicted compound-target interactions. Results: All extracts significantly reduced serum TC (↓ 27–33%), TG (↓ 29–38%), AST/ALT (↓ 22–30%), and DAO (↓ 35–42%) versus controls (p < 0.05). They improved hepatic steatosis, enhanced intestinal barrier function, and modulated gut microbiota (↑ α-diversity, ↓ Firmicutes/Bacteroidetes ratio). Transcriptomics revealed PPAR signaling as the core pathway: SJGS/SJGJ downregulated fatty acid oxidation genes (ACSL1, ACOX1, ACADM), while SJY upregulated APOA1 (2.3-fold). LC-MS identified 33–48 compounds/part, with seven shared constituents. Network analysis prioritized three flavonoids (pinocembrin, luteolin, galangin) targeting TNF, AKT1, and PPAR pathways. Conclusions: The findings suggest A. japonica extracts ameliorate hyperlipidemia through distinct mechanisms—SJGS/SJGJ may inhibit fatty acid oxidation, while SJY potentially enhances APOA1-mediated clearance. Shared flavonoids likely contribute to these effects via PPAR signaling, supporting its traditional use. This study provides a scientific basis for the sustainable utilization of A. japonica resources. Full article

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulators in plant immune responses, yet their roles in rice resistance against Magnaporthe oryzae (M. oryzae) remain inadequately explored. In this study, we integrated translatome data with conventional genome annotations to construct an optimized protein-coding dataset. Subsequently, we developed a robust pipeline (“RiceLncRNA”) for the accurate identification of rice lncRNAs. Using strand-specific RNA-sequencing (ssRNA-seq) data from the resistant (IR25), susceptible (LTH), and Nipponbare (NPB) varieties under M. oryzae infection, we identified 9003 high-confidence lncRNAs, significantly improving identification accuracy over traditional methods. Among the differentially expressed lncRNAs (DELs), those unique to IR25 were enriched in the biosynthetic pathways of phenylalanine, tyrosine, and tryptophan, which suggests that they are associated with the production of salicylic acid (SA) and auxin (IAA) precursors, which may be involved in defense responses. Conversely, DELs specific to LTH primarily clustered within carbon metabolism pathways, indicating a metabolic reprogramming mechanism. Notably, 21 DELs responded concurrently in both IR25 and LTH at 12 h and 24 h post-inoculation, indicating a synergistic regulation of jasmonic acid (JA) and ethylene (ET) signaling while partially suppressing IAA pathways. Weighted gene co-expression network analysis (WGCNA) and competing endogenous RNA (ceRNA) network analysis revealed that key lncRNAs (e.g., LncRNA.9497.1) may function as miRNA “sponges”, potentially influencing the expression of receptor-like kinases (RLKs), resistance (R) proteins, and hormone signaling pathways. The reliability of these findings was confirmed through qRT-PCR and cloning experiments. In summary, our study provides an optimized rice lncRNA annotation framework and reveals the mechanism by which lncRNAs enhance rice blast resistance through the regulation of hormone signaling pathways. These findings offer an important molecular basis for rice disease-resistant breeding. Full article

Flavor formation in citrus fruit is governed by complex and dynamic changes in primary and secondary metabolism during development and ripening. Here, we integrated metabolomic, hormonal, and transcriptomic analyses to elucidate the regulatory landscape underlying soluble sugar and organic acid metabolism in ‘Kiyomi’ citrus fruit. A total of 1679 metabolites were identified, revealing stage-specific reprogramming of metabolic pathways, including a sharp decline in citric acid after 90 days after flowering (DAF) and peak accumulation of sucrose at 180 DAF. Hormonal profiling showed that abscisic acid (ABA) progressively accumulated from 120 to 210 DAF, while 1-aminocyclopropane-1-carboxylic acid (ACC) peaked at 120 DAF and declined thereafter, suggesting distinct and temporally coordinated roles in ripening regulation. Transcriptomic profiling uncovered widespread temporal shifts in gene expression, with the most pronounced changes occurring between 180 and 210 DAF. Co-expression network analysis identified gene modules associated with sugar and acid accumulation, and highlighted transcription factors from the ERF, MYB, NAC, and HSF families as candidate regulators of ripening-related metabolic transitions. These findings provide a comprehensive framework for understanding the coordinated molecular and metabolic programs underlying flavor development in non-climacteric citrus fruit and offer candidate genes for the genetic improvement of fruit quality. Full article

Xylazine abuse is emerging as a global problem, whereas the toxic mechanisms of xylazine poisoning are seldom studied. The present study aims to assess the heart injury in xylazine poisoning and uncover the underlying mechanism. Forty male SD rats were randomly dived into four groups: control (saline), low dose (10 mg/kg xylazine), median dose (20 mg/kg xylazine) and high dose (40 mg/kg xylazine). The rats were injected with the drug intraperitoneally for 28 consecutive days, and then cardiac ultrasound examination was performed and serum and heart tissues were collected. Genomic, proteomic, and metabolic omics analyses were conducted. ELISA, RNA sequencing, histopathology examination, RT-qPCR, and Western blot were performed. Repeated injection of xylazine led to a decrease in the expression of cardiac output (CO), ventricular systole (VS), and ventricular diastole (VD), while concurrently elevating the levels of lactate dehydrogenase (LDH), creatine kinase myocardial band (CK-MB), and cardiac troponin T (c-TNT) in the serum. HE staining analysis showed evidence of contraction band necrosis, interstitial fibrosis, and infiltration by inflammatory cells in animals with xylazine poisoning. The modified genes, proteins, and metabolites were gathered, and the integration of transcriptomic, proteomic, and metabolic networks identified 25 overlapping pathways between the differentially expressed genes and metabolites (DEGs-DEMs) and the differentially expressed proteins and metabolites (DEPs-DEMs) joint pathways. The majority of these pathways pertained to the metabolism of sugars, amino acids, and fats. The proteins associated with fructose and mannose metabolism, as well as cholesterol metabolism, were validated, thereby substantiating their pivotal role in the development of xylazine-induced cardiac injury. Repeated injection of xylazine impaired heart function and the metabolism of fructose and mannose. Cholesterol metabolism pathways were critical in the process of xylazine-induced heart injury. Full article

Drought stress poses a significant threat to olive cultivation in Mediterranean regions. This study investigated the resilience and functional adaptation of root-associated and rhizosphere soil microorganisms of four olive cultivars under contrasting water regimes (irrigated vs. drought) across seasons. Using a combination of amplicon-targeted metagenomics, phylogenetic analysis, and text mining of the scientific literature, we identified a conserved core microbiome and revealed that drought stress significantly alters the structure of root-associated—but not rhizosphere soil—bacterial communities. Potential functional profiling indicated that drought conditions enriched for genes involved in stress response pathways, including branched-chain amino acid transport, glutathione S-transferase activity, thioredoxin reductase, and chemotaxis. Text mining co-occurrence networks highlighted strong associations between some key bacterial genera and plant growth-promoting functions like phytohormone production and biocontrol. Furthermore, we identified Solirubrobacter, Microvirga, and Pseudonocardia as the primary contributors to these drought-resilience functions. The stability of the soil microbiome suggests functional redundancy, whereas the restructuring of the root endophytic compartment indicates active plant selection for beneficial microbes. Our findings provide a foundation for developing tailored microbial consortia (SynComs) to enhance drought tolerance in olive trees and support sustainable agriculture in water-limited environments. Full article

Growth regulatory factors (GRFs) and growth-regulating interacting factors (GIFs) play significant roles in plant growth, development, and environmental stress responses. Previous studies have reported the functions of GRF and GIF genes in model plants such as Arabidopsis and rice. Nevertheless, the GRF and GIF genes remained unexplored in cassava. Cassava (Manihot esculenta Crantz) is an important tropical economic crop. Its starchy storage roots serve as a major source of food and industrial raw materials, while its protein-rich leaves are widely consumed as leafy vegetables in Africa and other regions, offering high nutritional value and significant horticultural potential. This study identified 28 MeGRFs distributed on 13 chromosomes and 5 MeGIFs on 4 chromosomes through bioinformatic analysis and expression profiling. Promoter analysis uncovered cis-acting elements associated with growth, hormone signaling, and biotic stress responses. Under different tissues and biotic (e.g., cassava bacterial blight, CBB) and abiotic (e.g., drought, low temperature) stress conditions, GRF and GIF genes exhibited differential expression patterns. Real-time quantitative PCR analysis showed a significant expression for 11 MeGRFs and 3 MeGIFs under the Xanthomonas phaseoli pv. manihotis (Xpm) treatment. VIGS functional validation demonstrated that MeGRF28 and MeGIF4 could enhance cassava resistance to bacterial blight, and protein–protein interaction network analysis suggested that they may form a core GRF-GIF complex. This study provides a theoretical basis for understanding the functional evolution of the GRF and GIF gene families in cassava and their roles in horticultural trait development and stress resistance mechanisms. Full article