Search Results (27,681)

Seasonal drought constitutes a major abiotic stress limiting the growth and yield of pineapple, a globally important Crassulacean acid metabolism (CAM) crop. The sucrose catabolism mediated by cell wall invertase (CWIN) plays a vital role in regulating plant growth and development, as well as adaptive responses to abiotic stresses. Invertase inhibitors (INHs) serve as specific post-translational regulators that modulate CWIN enzymatic activity. However, the INH family has not been systematically characterized in pineapple, and its functional roles in mediating sucrose metabolism and drought resistance remain elusive. In this study, three AcINHs were identified from the pineapple genome, followed by comprehensive analyses of their gene structures, phylogenetic relationships, homology characteristics and protein structures. Structural analysis revealed that all AcINH members harbor conserved motifs 1, 2, 3, 5 and 9, whereas only AcINH3 possesses motif 7. Expression analysis showed that only AcINH3 was significantly transcriptionally induced by drought stress among all family members. Functional validation demonstrated that AcINH3 knockout markedly elevated CWIN activity in pineapple seedling leaves, facilitating hexose accumulation and promoting plant growth and development. Moreover, AcINH3-edited lines exhibited enhanced drought resistance, accompanied by increased accumulation of soluble sugars (sucrose, glucose, fructose), abscisic acid (ABA), and proline (PRO), reduced malondialdehyde (MDA) content, and enhanced peroxidase (POD) activity. Biochemical assays further verified a direct physical interaction between AcINH3 and AcCWIN1, which mediates sucrose metabolism and drought stress responses. Collectively, this study identifies a novel AcINH3–AcCWIN1 post-translational module that modulates sugar metabolism and drought tolerance in pineapple, providing critical mechanistic insights for CAM plants. Our findings highlight AcINH3 as a promising target for genome-editing breeding to enhance drought resistance in CAM crops. Full article

A 56-day feeding trial was conducted to evaluate the effects of varying dietary lipid and starch levels on growth performance, biochemical components, and hepatic glycolipid metabolism in hybrid grouper. Nine isonitrogenous diets were formulated to contain three levels of lipid (6%, 10%, or 14%) and starch (14%, 21%, or 28%) using a 3 × 3 factorial design. Juvenile fish (initial body weight: 19.06 ± 0.03 g) were randomly allocated to 27 floating net cages (25 fish per cage, three replicates per diet) in an indoor seawater recirculation system and hand-fed to apparent satiation twice daily. Two-way ANOVA was conducted to check treatment effects of dietary lipid and starch levels. No interaction effect between lipid and starch on growth and feed utilization was observed across all treatments; however, significant interactions between the two were observed for condition factor (CF), and some serum biochemical indicators and some hepatic glycolipid metabolic enzyme activities. Growth rate, specific growth rate, and feed efficiency (FE) exhibited a declining trend with increasing dietary lipid levels (p < 0.05). Conversely, hepatosomatic index (HSI), viscerosomatic index (VSI), condition factor, hepatic lipid and glycogen contents, muscle lipid content, serum triglyceride and high-density lipoprotein cholesterol contents, as well as hepatic carnitine palmitoyltransferase 1 (CPT-1) and lipoprotein lipase (LPL) activities, showed an increasing trend (p < 0.05). As lipid levels increased, serum total cholesterol (TC) and total protein (TP) contents dropped to a minimum at the intermediate lipid level (10%) and then rose, regardless of starch level. Hepatic fructose-1,6-bisphosphatase (FBP) activity increased significantly when lipid level rose from 6% to 10% (p < 0.05). With increasing dietary starch levels, HSI, VSI, hepatic and muscle glycogen contents, and serum low-density lipoprotein cholesterol content increased, while FE and serum TP content decreased (p < 0.05). Hepatic CPT-1, LPL, FBP, and pyruvate kinase activities were significantly enhanced when starch levels increased from 14% to 21% or 28% (p < 0.05). Serum aspartate aminotransferase activity was significantly higher in fish fed 14% lipid compared to those fed 6% or 10% lipid. These findings indicate that there is no interaction of dietary lipid and starch on growth and feed utilization, but high dietary lipid (14%) may enhance hepatic lipid oxidation while suppressing glycolysis, thereby limiting growth and promoting hepatic lipid deposition. The results provide a practical reference for optimizing dietary lipid and starch levels in cost-effective feed formulations for hybrid grouper. Full article

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic lipid accumulation and can progress to severe liver injury. Kaempferol (KPF), a plant-derived flavonoid, exhibits lipid-regulatory properties. Tripartite motif-containing protein 56 (TRIM56), an E3 ubiquitin ligase, has been reported to interact with fatty acid synthase (FASN) and limit hepatic lipogenesis. This study investigated whether KPF alleviates NAFLD through modulation of TRIM56-associated lipid metabolic pathways. Molecular docking, molecular dynamics simulations, and cellular thermal shift assays (CETSA) were employed to evaluate the interaction between KPF and TRIM56. High-fat diet-induced NAFLD mice and fatty acid-treated HepG2 cells were used to assess the effects of KPF on hepatic lipid accumulation. Histological analysis, lipid profiling, Oil Red O staining, Western blotting, immunofluorescence, and quantitative PCR were performed. Endogenous co-immunoprecipitation examined the association between TRIM56 and FASN, and siRNA-mediated knockdown of TRIM56 evaluated its functional contribution. KPF significantly reduced serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, ameliorated hepatic steatosis in vivo, and decreased intracellular lipid accumulation in vitro. In silico and CETSA analyses supported the engagement of TRIM56 by KPF. KPF restored TRIM56 expression under steatotic conditions, whereas TRIM56 silencing attenuated its lipid-lowering effects. TRIM56 was confirmed to associate with FASN, and KPF treatment suppressed multiple lipogenic enzymes. These findings indicate that KPF alleviates hepatic steatosis, at least in part, through modulation of TRIM56-associated lipogenic pathways, highlighting TRIM56 as a potential therapeutic target in NAFLD. Full article

Porcine epidemic diarrhea virus (PEDV) causes lethal enteritis in neonatal piglets, yet the mechanisms underlying rapid intestinal injury remain unclear. In particular, it is unknown whether different regulated cell death pathways act separately or cooperatively to worsen mucosal damage. To address this question, we performed multi-omics analyses of infected intestinal tissues and found concurrent activation of pyroptosis and ferroptosis during PEDV infection. PEDV infection activated the Caspa-se-1/GSDMD pathway in the duodenum and jejunum, as shown by generation of the Caspase-1 p20 fragment and cleavage of GSDMD into its active N-terminal form, indicating pyroptosis. At the same time, infected tissues displayed key features of ferroptosis, including weakened antioxidant defenses, increased lipid peroxidation, iron accumulation, lipid remodeling, and dysregulated ACSL4 and GPX4 expression. These two processes were closely linked and together contributed to tight junction disruption and barrier instability. Molecular docking further suggested that PEDV NSP1 and S proteins may interact with Caspase-1, providing a possible explanation for pyroptosis induction. Correlation analysis also showed strong associations between pyroptosis-related genes and ferroptosis-associated metabolites. Overall, our findings indicate that pyroptosis and ferroptosis cooperate to drive PEDV-induced intestinal inflammation and barrier damage, highlighting their joint inhibition as a potential strategy to reduce PEDV pathogenicity. Full article

Background/Objectives: Synthetic stimulants represent the most prevalent subclass on the new psychoactive substances (NPSs) market. However, the toxicokinetic properties of M-ALPHA, a regioisomer of MDMA and N-methyl-cyclazodone a pemoline derivative, are not yet characterized. Methods: Therefore, this study investigated the metabolism of both NPSs in pooled liver S9 fraction and rat urine, characterized cytochrome P450 (CYP) kinetics and plasma protein binding (PPB), and assessed the CYP inhibition potential of M-ALPHA, using high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (HPLC-HRMS/MS). Results: Four metabolites of M-ALPHA were detected including one phase I and three phase II metabolites, resulting from demethylenation followed by subsequent methylation or glucuronidation. For N-methyl-cyclazodone, one phase I metabolite formed via N-demethylation was identified. The primary enzymes involved in M-ALPHA metabolism were CYP2B6 and CYP2D6. Notably, M-ALPHA inhibited these enzymes to a strong or moderate extent, respectively. In contrast, the metabolism of N-methyl-cyclazodone was primarily mediated by CYP2A6. PPB studies indicated low-to-moderate binding for both compounds, suggesting that significant protein-binding interactions are unlikely. Conclusions: As M-ALPHA only formed metabolites that overlapped with those of MDMA, differing only by minor retention time shifts, reliable HPLC-HRMS/MS-based identification may be challenging in clinical and forensic toxicology settings as well as doping analysis. Furthermore, drug–drug interactions following polydrug use cannot be excluded for either NPS, particularly when co-ingested with other CYP substrates metabolized by the same isoforms. Full article

Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) represent fundamental cellular adaptive mechanisms that maintain protein homeostasis and metabolic balance. Many RNA viruses, particularly flaviviruses such as dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), yellow fever virus (YFV), and Japanese encephalitis virus (JEV), extensively remodel the ER to establish replication compartments and assemble progeny virions. This massive reorganization disrupts ER homeostasis, leading to UPR activation. Emerging evidence reveals that flaviviruses not only trigger but also manipulate the three UPR branches—PERK, IRE1, and ATF6—to optimize viral translation, replication, and egress. In parallel, flavivirus infection profoundly alters host lipid metabolism and promotes dynamic changes in lipid droplets (LDs), key organelles that mediate lipid storage and serve as scaffolds for viral replication and assembly. The UPR intimately connects to LD biogenesis through transcriptional and translational programs mediated by XBP1, ATF4, and ATF6, thereby coupling ER stress responses to lipid remodeling and energy homeostasis. This intricate crosstalk between UPR and LDs creates a metabolic and structural niche favorable for viral replication but detrimental to host cell integrity. This review provides a comprehensive analysis of the molecular mechanisms by which flaviviruses exploit ER stress and the UPR to reprogram lipid metabolism and LD dynamics. We highlight the dual role of UPR signaling in promoting adaptive lipid synthesis and initiating cell death under prolonged stress, discuss recent insights into ER–LD interactions during flavivirus infection, and explore therapeutic opportunities targeting UPR–lipid metabolic pathways as broad-spectrum antiviral strategies. Understanding this interconnected network will advance our knowledge of viral pathogenesis and identify new avenues for host-directed antiviral intervention. Full article

The immune system plays a pivotal role in the maintenance of homeostasis and protection from pathogens. With increasing public interest in immune health, functional foods and herbal formulations are gaining attention as potential immunomodulators. Therefore, we aimed to investigate the combined immune-enhancing effects of HemoHIM (HIM) and Hwaljingigo (HGG) through combination treatment based on the recommended daily intake in RAW 264.7 macrophages. Cell viability, nitric oxide (NO) production, and cytokine (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) expression levels were assessed using the XTT, Griess, and enzyme-linked immunosorbent assay (ELISA), respectively. Immunoblotting was conducted to confirm changes in protein expression. Neither HIM nor HGG was cytotoxic at any of the tested concentrations. Both the single and combination treatments increased NO production and cytokine expression in a concentration-dependent manner. Furthermore, the combination of HIM (one sachet) and HGG (three sachets) resulted in the highest levels of NO and cytokine production. Bliss Independence analysis revealed synergistic interactions for IL-1β and IL-6, while NO and TNF-α showed additive effects. These findings suggest that the combination of HIM and HGG enhances immune responses by stimulating macrophage activity, thereby supporting the potential application of multi-herbal formulations as functional immunomodulatory agents. Full article

Chronic kidney disease (CKD) is a progressive global health challenge. While empagliflozin, a selective SGLT2 inhibitor, is known to attenuate CKD progression through mechanisms beyond glycemic control, the precise molecular pathways remain incompletely characterized and warrant further investigation. This study employed an integrated network pharmacology and molecular docking approach to elucidate the multi-target mechanisms of empagliflozin in CKD. Initial evaluation demonstrated that empagliflozin exhibits favorable physicochemical properties, drug-likeness, and ADMET profiles, supporting its potential as an effective orally administered therapeutic option for CKD management. Network analysis identified 221 shared molecular targets between empagliflozin and CKD-associated genes. Topological analysis of the protein–protein interaction (PPI) network revealed ten critical hub proteins—GAPDH, IL6, EGFR, HSP90AA1, NFKB1, HSP90AB1, MTOR, MAPK3, IL2, and PIK3CA—which serve as key regulators in CKD pathophysiology. Gene Ontology and KEGG pathway enrichment analyses indicated that these shared targets are significantly involved in phosphorylation, signal transduction, and central signaling cascades associated with CKD progression, including the PI3K-Akt, FoxO, HIF-1, and AGE-RAGE pathways. Molecular docking simulations corroborated empagliflozin’s multi-target affinity, demonstrating particularly strong binding energies toward HSP90AB1 (−10.85 kcal/mol), MAPK3 (−9.46 kcal/mol), and EGFR (−9.38 kcal/mol). Empagliflozin maintained stable hydrogen bonding throughout the 200-ns molecular dynamics simulation, primarily with GLN18, GLU42, SER45, ASN46, ASN101, GLY130, and TYR134, underscoring its persistent and well-anchored interaction with HSP90AB1. Collectively, these findings provide crucial mechanistic insights, suggesting that empagliflozin might exerts therapeutic effects by modulating interconnected pathways regulating inflammation, oxidative stress, and metabolic homeostasis, thereby reinforcing its role as a comprehensive, multi-target therapeutic strategy for CKD management. Nonetheless, validation through in vitro experiments remains necessary. Full article

CARP-1, a perinuclear phospho-protein, is a biphasic regulator of cell survival and apoptosis signaling. We previously found that UV cross-linking of proteins from HeLa cervical cancer cells resulted in STAT3 interacting with the CARP-1 (614–638) peptide. Mutagenesis and co-IP-WB experiments revealed that CARP-1 interacts with a 40-amino-acid epitope from positions 441–480 (CE Epitope) located in the STAT3 DNA-binding domain. Overexpression of mutant STAT3 with in-frame deletion of the CE epitope (Gst-STAT3 (ΔCE) mutant), but not Gst-STAT3 (WT), failed to translocate to the nucleus in IL-6-treated cells. The small GTPase p21Rac1 interacts with and regulates STAT3 activation and nuclear translocation. Here we report the interaction of p21Rac1 with the CE epitope of STAT3 and the CARP-1 (600–650) region, suggesting that CARP-1 is part of a dynamic STAT3-p21Rac1 complex that functions in STAT3 activation and nuclear translocation. Expression of a STAT3 (ΔCE) mutant abolished STAT3 Y705 phosphorylation in cells that were treated with EGF or IL-6. Fine mapping revealed that scrambling the CE epitope peptide or a small peptide from positions 456–465 within the CE epitope resulted in abrogation of STAT3 Y705 phosphorylation by IL-6. Moreover, STAT3 phosphorylation by EGF or IL-6 was diminished in multiple CARP-1 null cancer cells. Importantly, incubation of a TAT-tagged STAT3 (454–467) peptide but not its scrambled version resulted in a reduction in STAT3 Y705 phosphorylation by IL-6/EGF. Taken together, our data demonstrates that the STAT3 CE epitope interacts with CARP-1 and p21Rac1, harbors novel sequences that activate STAT3 and promotes its nuclear translocation by IL-6/EGF. Full article

The estuarine and coastal regions of India and Taiwan are under increasing threat from pollutants such as microplastics (MPs) and heavy metals including cadmium (Cd). These contaminants are known to have adversely affect biodiversity and water quality. In this study, the combined toxic effects of polyethylene microplastics (PE-MPs) and Cd were evaluated using Poecilia sphenops, a euryhaline fish species, selected for its adaptability to varying salinity conditions. P. sphenops were exposed to Cd (20, 40, and 60 μg/L), MPs (8, 16, 24 mg/L), and co-exposure combinations ranging from Cd 5 μg/L + MPs 4 mg/L to Cd 20 μg/L + MPs 16 mg/L Results showed significant (p< 0.05) negative effects on growth parameters including body weight gain, specific growth rate (SGR), and survival rate. Hematological analysis revealed significant (p< 0.05) decreases in hemoglobin (Hb), red blood cells (RBCs), and white blood cells (WBCs), indicating impaired oxygen transport and compromised immune function. Elevated blood glucose levels indicated physiological stress, while reduced total protein levels suggested a compromised nutritional status. Antioxidant enzyme activities, including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx), were significantly (p < 0.05) decreased in the toxicant-treated groups compared with the control. Digestive enzyme activities (proteases, amylases, and lipases) were also reduced, suggesting impaired digestion and nutrient assimilation. The study also included a comparative assessment of water quality between the exposed and control tanks. Water quality parameters such as turbidity, salinity, hardness, alkalinity, chloride, fluoride, and total suspended solids (TSSs) were elevated in the toxicant-treated media, accompanied by a notable decline in dissolved oxygen (DO) levels. These findings highlight the urgent need for integrated pollution control and water quality monitoring, particularly in coastal regions vulnerable to desalination discharges and plastic contamination. Sustainable management strategies must address these complex interactions between multiple pollutants to protect aquatic ecosystems. Full article

Background: Chromosomal rearrangements involving lysine methyltransferase 2A (KMT2A) define a genetically distinct subset of acute myeloid leukemia (AML) in 10% of cases in adult patients; the frequency of KMT2A-r is higher in pediatric AML. Translocations involving the KMT2A locus at chromosome 11q23 result in the formation of a chimeric oncogene partner, where the N-terminal part of KMT2A is fused to a variety of translocation partners. The leukemogenic activity of KMT2A-fusion partners is related to their capacity to hyperactivate the expression of HOX-A and MEIS1 target genes, which stimulate the proliferation of hematopoietic stem cells. The oncogenic activity of KMT2A fusion proteins requires the binding with Menin, and this interaction can be targeted pharmacologically by small molecules acting as potent and selective Menin inhibitors. Methods: A search of the literature showed a marked development of experimental studies exploring the molecular pathogenesis of AML with KMT2A-r and of clinical studies evaluating new induction intensive treatments and the development of a targeted therapy based on Menin inhibitors. Results and Conclusions: In the present review article, we summarize our current understanding of the biology of KMT2A-r in AML development and the recent consistent progress made in the treatment of KMT2A-r AML through new chemotherapy regimens and targeted therapy using Menin inhibitors. However, the prognosis of older KMT2A-r AML patients remains poor and could be improved by drug combination studies including Menin inhibitors. Many encouraging observations derived from ongoing clinical trials with Menin inhibitors need to be confirmed through randomized clinical trials. Full article

Background: Aberrant protein O-fucosylation mediated by protein O-fucosyltransferase 1 (POFUT1), has emerged as a hallmark of tumorigenesis that regulates key signaling pathways, including Notch, which is frequently dysregulated in cancers. Protein O-fucosylation, catalyzed by POFUT1, regulates Notch signaling and has been implicated in individual cancers, but its pan-cancer expression patterns, clinical significance, and relationship to tumor immunity remain incompletely characterized. Methodology: We conducted a multi-omics bioinformatics analysis using TCGA and other public datasets to evaluate POFUT1 expression across 33 cancer types (n > 10,000). Differential expressions, tumor stage correlations, and survival outcomes were assessed. Immune cell infiltration was estimated using SangerBox and TIMER algorithms, while promoter methylation patterns were analyzed through UALCAN. Functional enrichment and protein–protein interaction networks were constructed to elucidate functional mechanism. Western blot validation in prostate and ovarian cancer cell lines confirmed our computational analysis. Results: POFUT1 showed significant overexpression in 16 of 33 cancer types (FDR-adjusted p < 0.05), with the highest elevation in BRCA (breast invasive carcinoma; log2FC = 2.31) and LUAD (lung adenocarcinoma; log2FC = 2.1). A high POFUT1 expression correlated with poor overall survival in eight cancer types (HR range: 1.8–3.2, p < 0.01) and disease-free survival in seven cancers. POFUT1 levels positively correlated with myeloid-derived suppressor cells (MDSCs) infiltrating in 15 cancer types, while inversely correlated with natural killer T (NKT) cells presence in 15 cancers (mean R = −0.34, p < 0.05), indicating an association with immunosuppressive microenvironments. Promoter hypomethylation in tumors suggested epigenetic dysregulation as a potential driver of its overexpression. Western blot analysis confirmed POFUT1 protein upregulations in prostate and ovarian cancer cell lines (1.7–2.1-fold. p < 0.01), corroborating transcriptomic findings. Conclusion: This pan-cancer study establishes POFUT1 as a critical oncogenic factor linked to aggressive disease, immune evasion, and poor prognosis. Its consistent overexpression and functional impact highlight its potential as a biomarker and target for anticancer therapy. While these computational findings require experimental validation, POFUT1 emerges as a candidate biomarker warranting functional studies and potential therapeutic targeting. Full article

Canola meal, with environmentally friendly attributes, lower cost, and previous studies, is an interesting proteic source to partially replace the soybean meal for poultry nutrition. For that, in this work we aimed to investigate canola meal as a partial replacement of soybean meal in finishing poultry diets (21 to 49 days) on the productive performance, also including the impact on the quality, nutritional attributes and antioxidative status of valuable cuts of meat. Ninety-six 21-day-old chickens were assigned to four experimental diets (24/diet), with increasing doses of canola meal (CM 0, 2.5, 5 and 10%). Daily consumption, weekly live weight and post mortem carcass weight and yield were determined. At 24 h post mortem, pH, color (CIE L, a*, b*) and drip loss were measured in the breast, drumstick and thigh cuts. Fatty acid composition and health lipid indexes were also determined in the fresh cuts. The oxidative status of lipids and proteins, polyphenol and flavonoids content in fresh and in stored (7 days-display at 4–6 °C) in vacuum packaged cuts were determined. Including CM, up to 10%, the feed intake and growth of birds was not affected (p = 0.74 and p = 0.87 respectively). In meat, CM significantly decreased the drip loss (p < 0.05), the pH in breast and thigh (p = 0.01 and p = 0.05 respectively), a lower L and b in thigh and increased PUFAs in more oxidative cuts, with a strong interaction between dose and muscle type. There was no effect on lipid oxidation while carbonyls decrease at a 2.5% dose in fresh and stored cuts but there is an increase with higher ones. Flavonoids raise the maximum deposition in meat at 5% CM. In conclusion, CM can be included in finishing poultry diets, but high doses must to be adequately managed if performance and quality of meat criteria are considered together. Full article

Neuroblastoma is characterized by noticeable resistance to chemotherapy, largely driven by the ability of tumour cells to reorganize stress-adaptive signalling networks rather than relying on single oncogenic drivers. We conducted a study to investigate the pharmacological mode of action of doxorubicin in modifying adaptive signalling pathways in SH-SY5Y neuroblastoma cells, and whether the capacity of plant metabolites can exploit emergent biochemical vulnerabilities. Transcriptomic profiling through RNA sequencing conducted 48 h post-doxorubicin exposure unveiled the organized disruption of pathways linked with amyloidogenic processes, oncogenic signalling pathways, oxidative stress, and DNA repair. The protein–protein interactions, coupled with Kyoto Encyclopedia of Genes and Genomes pathway evaluations, revealed five network-central-hubs: BRAF, GSK3β, PARP1, BACE1, and MAOB. Structural docking integrated with 200 ns molecular dynamics simulations illustrated binding stability across multiple targets driven by three metabolites, Lactol binding to BRAF (−54.13 kcal/mol) and MAOB (−39.08 kcal/mol), Amino(1H-indol-2-yl)acetic acid to BACE1 (−41.07 kcal/mol) and GSK3β (−47.38 kcal/mol), and Quercetin-3-(6″-malonyl-glucoside) binding to PARP1 (−46.03 kcal/mol). In vitro Cell Counting Kit-8 proliferation assays validated the significant anti-neuroblastoma efficacy, with the lowest IC₅₀ (0.2397 µM) being exhibited by Amino(1H-indol-2-yl)acetic acid, followed by Lactol (1.226 µM) and Quercetin-3-(6″-malonyl-glucoside) (1.301 µM), which mirrored the cytotoxic action of doxorubicin (1.306 µM). These results suggest that plant-derived metabolites may interact with stress-adaptive signalling pathways connected with neuroblastoma. However, direct experimental validation of target engagement and pathway modulation will be required to confirm these predicted interactions. Full article

Sucrose synthase (SUS) is a key enzyme in plant carbon metabolism, catalyzing the reversible interconversion between sucrose + uridine diphosphate (UDP) and UDP-glucose (UDP-Glc) + fructose. It plays a central role in carbon flux allocation, cell wall and starch synthesis, as well as plant development and stress responses. SUS is encoded by a multigene family whose members exhibit significant functional diversification and expression specificity across species, tissues, and subcellular compartments. This review systematically summarizes the physiological functions of SUS in source–sink regulation, seed filling, and rapidly growing tissues; describes the organ-specific expression patterns and diverse subcellular localizations of different isoenzymes in Arabidopsis and major crops; and elucidates the phylogenetic pattern of the SUS gene family into three evolutionary clades—SUS I, SUS II, and SUS III—based on a comparative analysis of selected angiosperm species. Furthermore, it integrates the multi-level regulatory mechanisms of SUS, including transcriptional and post-transcriptional regulation, as well as the dynamic control of enzyme activity, stability, and subcellular localization through post-translational modifications such as phosphorylation and ubiquitination and protein interactions. Finally, this study identifies gaps in current research regarding ubiquitination mechanisms, metabolic network integration, and crop applications. It envisions SUS-centered molecular breeding strategies, informed by integrative regulatory genomics, multi-omics, and genome editing, to redirect crop carbon fluxes and thereby enhance yield, improve quality traits, and increase stress tolerance. Full article