Antibiotic treatment is often necessary to eliminate life-threatening bacterial infections. However, these treatments can alter production of bacterial extracellular vesicles (BEVs), which often contain pro-inflammatory biomolecules. In this study, we examined how the clinically relevant antibiotics meropenem, tobramycin, and ciprofloxacin impacted BEV production from a urinary tract infection-associated Escherichia coli strain (CFT073 [WAM2267]) and a meningitis-associated strain (K1 RS218). BEVs from both strains caused a dose-dependent increase in expression of intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells, priming the endothelium for interactions with immune cells. Blockade of toll-like receptor 4 revealed that this receptor was responsible for BEV-endothelial interactions. Treatment with meropenem, a β-lactam antibiotic, increased production of BEVs from strain K1 RS218. Furthermore, meropenem treatment caused strain CFT073 [WAM2267] to produce BEVs with heightened stimulatory capacity, possibly by amplifying the content of lipoprotein Lpp in these BEVs as measured by mass spectrometry. To our knowledge, this is the first study examining the interplay between antibiotic treatment and the effects of the resulting BEVs on endothelial ICAM-1 expression. Our results indicate treatment risks of certain antibiotics against specific strains of E. coli and could help identify therapeutic targets to reduce BEV-mediated endothelial stimulation during infection.

Animal venoms are rich in bioactive peptides with potential therapeutic properties. Among marine toxins, jellyfish venoms are underexplored for anti-inflammatory applications. This study aims to identify and evaluate a peptide derived from the jellyfish toxin CfTX-B, for its anti-inflammatory potential.

Although androgen receptor (AR) inhibitors such as enzalutamide are initially effective in castration resistant prostate cancer through suppression of AR signaling pathway, acquired resistance invariably develops, presenting a significant therapeutic challenge. Understanding the mechanisms of enzalutamide resistance (ENZR) is essential for developing improved therapeutic strategies. Here, we demonstrated that ZNF711 was significantly overexpressed in ENZR, and high ZNF711 levels correlated with poor clinical outcomes. Functionally, ZNF711 promoted ENZR progression both in vitro and in vivo. Mechanistically, ZNF711 directly bound to the AR promoter, transcriptionally upregulating AR expression. ZNF711 knockdown markedly reduced AR chromatin occupancy at target loci. Additionally, ZNF711 formed a complex with BMI1 and AR, enhancing AR signaling pathway by suppressing CpG methylation at the promoter of AR and its downstream target genes (e.g., KLK3, TMPRSS2), thereby potentiating AR transcriptional activity. Notably, targeting ZNF711 with antagonistic chimeric siRNA restored enzalutamide sensitivity in vivo. Collectively, our findings establish ZNF711 as a critical regulator of ENZR that promotes resistance by dually modulating the AR signaling pathway via transcriptional activation and epigenetic demethylation. Targeting the ZNF711-AR axis represents a novel therapeutic strategy to overcome ENZR in prostate cancer.

MUC14/Endomucin, a transmembrane mucin, is a potential prognostic biomarker in malignancies. This study aimed to elucidate the functional impact of MUC14 on tumor proliferation, migration, immune microenvironment modulation, and cisplatin response in lung adenocarcinoma (LUAD), and investigate its molecular mechanisms. LUAD cell lines with MUC14 overexpression (MUC14-OE) or silencing were constructed. Malignant behaviors were assessed via CCK-8, Transwell, and colony formation assays. Immune cell infiltration was quantified by CD3+/CD8 + immunohistochemistry. Subcutaneous xenograft and tail-vein metastasis murine models evaluated in vivo tumor progression and cisplatin responsiveness. Mechanisms were characterized using FRET and western blotting. Multiplatform bioinformatics analysis of public databases correlated MUC14 expression with clinical outcomes, immune infiltration, and chemotherapy response. MUC14-OE inhibited LUAD cell proliferation, migration, colony formation, and adhesion, while silencing promoted these phenotypes. MUC14 expression positively correlated with CD3+/CD8 + T-cell infiltration. In vivo, MUC14-OE suppressed subcutaneous tumor growth, lung metastasis, and enhanced cisplatin efficacy. Mechanistically, MUC14 inhibited integrin α8β6 clustering, suppressing PI3K/AKT and MAPK/ERK signaling. Cisplatin sensitization involved JNK/c-Jun pathway activation. This study establishes MUC14 as a multifunctional tumor suppressor in LUAD. It inhibits integrin α8β6-mediated PI3K/AKT and MAPK/ERK signaling to suppress tumor growth, promotes CD8+ T-cell infiltration, and augments cisplatin sensitivity via the JNK/c-Jun pathway. These findings nominate MUC14 as a prognostic biomarker and therapeutic target, suggesting combinatorial strategies integrating immunotherapy and chemotherapy.

Esophageal cancer is a highly aggressive malignant tumor of the digestive tract, with significant heterogeneity in its pathogenesis and clinical manifestations. Despite advances in treatment strategies such as surgery, chemotherapy, and radiotherapy, the prognosis of esophageal cancer remains poor. In recent years, increasing evidence has shown that epigenetic regulation plays a critical role in the occurrence and development of esophageal cancer. Epigenetic mechanisms, including DNA methylation, histone modification, and non-coding RNA, can regulate gene expression without changing the DNA sequence and are involved in a variety of biological processes, including cell proliferation, apoptosis, and invasion. Abnormal epigenetic alterations are not only key drivers of tumorigenesis but also promising biomarkers and therapeutic targets. This review focuses on the epigenetic mechanisms involved in esophageal cancer and summarizes the latest progress in epigenetic-based therapeutic strategies, including the development and application of DNA methyltransferase inhibitors, histone deacetylase inhibitors, and drugs targeting non-coding RNAs. Moreover, it discusses the challenges and future prospects of epigenetic therapy in the clinical management of esophageal cancer.

Perfluorooctane sulfonate (PFOS) is a persistent and bioaccumulative member of the per- and polyfluoroalkyl substances (PFAS) family widely used in various industrial applications and consumer products. In this study we present a comprehensive analysis of the effects of PFOS exposure on zebrafish embryos with respect to possible role of the organic anion transporting polypeptide 1d1 (Oatp1d1) membrane transporter, focusing on the differential responses between wild-type (WT) and Oatp1d1 mutant embryos. Significant differences in mortality rates were observed, with LC50 values of 23.57 μM for WT and 16.71 μM for oatp1d1 mutants, indicating a higher susceptibility of the mutants to PFOS toxicity. Developmental abnormalities, particularly in the swim bladder, were more pronounced in mutant embryos. In addition, gene expression analysis showed changes in expression of genes involved in biotransformation processes, including members of the cytochrome P450 and glutathione S-transferase families. In summary, results of this study emphasize the complexity of PFOS-induced developmental toxicity mechanisms, implying important protective role of the Oatp1d1 transporter possibly related to detoxification processes or regulation of bioavailability. The findings improve our understanding of the toxicokinetic and toxicodynamic mechanisms of PFOS, emphasizing potential need for additional regulatory measures to address PFOS contamination and protect both aquatic life and human populations.

Proteus mirabilis is a uropathogen frequently implicated in catheter-associated urinary tract infections (CAUTIs), largely due to its ability to form biofilms and express multiple virulence factors. The limitations of conventional antibiotics, along with increasing resistance rates, necessitate the exploration of natural compounds with broader antimicrobial mechanisms against such pathogens. This study investigated the antibiofilm and anti-virulence potential of Juglone, a phytochemical derived from Juglans regia, against P. mirabilis. A series of in vitro assays demonstrated that Juglone not only inhibited bacterial proliferation in a dose- and time-dependent manner but also significantly restricted biofilm formation, as visualized by FE-SEM, while simultaneously impairing motility and reducing the secretion of critical virulence-associated enzymes. Membrane depolarization and altered membrane fluidity indicated compromised bacterial envelope integrity. Gene expression analysis using RT-qPCR further revealed the downregulation of multiple adherence- and virulence-associated genes. Complementing these findings, molecular docking and molecular dynamics simulations confirmed stable interactions between Juglone and the MrpH adhesin protein, highlighting its potential to interfere with host attachment mechanisms. Importantly, untargeted LC-MS-based metabolomic profiling revealed widespread metabolic reprogramming in Juglone-treated P. mirabilis, characterized by enhanced oxidative stress, redox imbalance, and suppression of core biosynthetic and energy-generating pathways. Taken together, these findings establish Juglone as a promising multi-target antimicrobial agent against P. mirabilis, with potential applications in the prevention of catheter-associated infections.

EphA2, a receptor tyrosine kinase, is overexpressed in various cancers. Its ligand-independent non-canonical signaling is pro-tumorigenic, and elevated EphA2 expression is associated with poor prognosis in patients. Although preclinical and clinical studies targeting EphA2 have been conducted as cancer therapeutics, its role in the DNA damage response remains elusive. This study examined the role of EphA2 in cell cycle progression in Adriamycin (ADR)-treated cells. ADR treatment transcriptionally upregulated EphA2 expression in a p53-independent manner. Suppression of EphA2 upregulation abrogated G2 arrest, as evidenced by reductions in both cyclin B1 accumulation and Wee1 inhibition-driven cell division. However, the 2N-G1 cell population remained low, with increased tetraploid cells. Time-lapse imaging revealed that tetraploid formation resulted from mitotic bypass rather than mitotic slippage or cytokinesis failure. EphA2 knockdown upregulated p21 expression together with p53, and p21 knockdown suppressed EphA2 knockdown-induced mitotic bypass. Monitoring fluorescence from a green fluorescent protein fusion with the cyclin B1 destruction box demonstrated degradation in interphase without cell division, suggesting premature activation of APC/CCdh1 in interphase. Notably, p21 upregulation following EphA2 knockdown was observed specifically in cervical cancer cell lines. Finally, ADR-induced suppression of cell proliferation was further enhanced by EphA2 knockdown and partially reversed by p21 knockdown. In conclusion, EphA2 suppression induces p21-dependent mitotic bypass and tetraploidization, leading to reduced cell proliferation. EphA2 upregulation following DNA damage may be pro-tumorigenic by maintaining G2 arrest to keep DNA damage at tolerable levels. These findings provide a rationale for combining EphA2 inhibition with DNA-damaging agents in certain cancer types.

Bladder cancer remains a major cause of global mortality with limited therapies. Here, we reported that epigenetic regulator EP300 acts as oncogenic role in bladder cancer. Public data show EP300 mutations correlated with better prognosis, while high EP300 expression predicted poor outcomes. Our clinical cohort demonstrated that EP300 expressed higher in tumors rather than adjacent tissues. Functionally, impairing of EP300 decreased both cell viability and organoids growth in bladder cancer cells. The selective EP300 inhibitor A485 similarly reduced bladder cancer cell growth in vitro and in vivo. Long-term treatment of A485 alleviated tumor invasion in a BBN-induced spontaneous bladder cancer mouse model. Bioinformatic analysis evaluated both basal/squamous-like markers and papillary-like markers were decreased in A485 treatment. Furthermore, downregulated genes by A485 are mainly related to cell cycle regulation. Mechanistically, A485 decreased the levels of EP300 and H3K27ac upon MYC enhancer, consequently inhibited MYC expression. Additionally, the MYC inhibitor demonstrated similar effects as A485 to decrease cell viability and organoid growth. Critically, in patient-derived organoids (PDOs), A485 selectively attenuated tumor organoid growth and reduced MKI67+ and CD44+ cell populations, sparing adjacent normal tissue organoids. Collectively, EP300 promotes bladder cancer progression by sustaining proliferation through MYC regulation, and its inhibitor A485 represents a promising targeted therapeutic candidate.

Microplastic (MP) pollution has emerged as a ubiquitous environmental threat, yet long-term transgenerational consequences remain poorly understood. This study investigated transgenerational epigenetic inheritance in Daphnia magna following exposure to polyethylene MP fragments containing benzophenone-3 (MP/BP-3). Four generations (F0-F3) were examined for 21 days each, with only F0 directly exposed to MP/BP-3. Population growth rates showed significant decreases in F0-F1, followed by recovery in F2-F3. Whole genome bisulfite sequencing revealed 492, 357, 351, and 681 differentially methylated genes in F0, F1, F2, and F3 generations, respectively. Remarkably, six genes remained hypomethylated through all four generations, including PAPSS1, ELP1, PRPL20, and IAPS5, encoding proteins involved in detoxification, development, and cellular stress, and cell adhesion. GO and KEGG pathway analyses consistently identified 'cell adhesion' and cardiovascular-related pathways as enriched through all generations, suggesting persistent predisposition to cardiac dysfunction. These findings demonstrate that single-generation MP exposure creates lasting molecular signatures that persist through unexposed offspring, fundamentally challenging current environmental risk assessment frameworks.

Microplastics threaten plant productivity and medicinal quality by disrupting physiological and metabolic functions. Using the medicinal herb Salvia miltiorrhiza, we established a controlled in vitro culture system with defined ploidy (diploid NY and triploid 810) to test how multi-walled carbon nanotubes (MWCNTs) mitigate polystyrene microplastics (PSMPs) stress in a ploidy-dependent manner, assessing impacts on regeneration, whole-plant growth, hairy-root metabolism and targeted gene expression. In hairy roots, PSMPs reduced dihydrotanshinone and salvianolic acid B contents by about 50 %, whereas MWCNTs restored and even enhanced metabolites with levels exceeding controls by more than 17 %. Targeted gene expression analyses showed that PSMPs downregulated key biosynthetic checkpoints for phenolic acids and tanshinones, while MWCNTs reactivated these pathways, with triploids showing greater recovery. PSMP exposure caused clear, dose-dependent inhibition of plant height and shoot induction: at 15 mg·L-1, plant height decreased by 40 % in NY and 33 % in 810, and shoot induction declined by more than 60 %. MWCNT co-treatments shortened shoot formation by six days, with triploid plants showing stronger recovery. PSMPs also increased reactive oxygen species by about 30 % and reduced photosystem II efficiency by 10 %, whereas 5 mg·L-1 MWCNTs lowered oxidative markers by nearly 20 % and restored photosynthetic performance to 95 % of control levels. Overall, MWCNTs mitigated PSMP-induced phytotoxicity by reducing internal PSMP accumulation and stabilizing redox, hormonal, photosynthetic, and developmental balance in a ploidy-sensitive manner. These findings provide a ploidy-aware, plant-compatible framework for understanding microplastic-induced phytotoxicity, suggesting practical strategies for mitigating microplastic hazards and safeguarding biomass and medicinal output in contaminated environments.

Quercetin (Que) possesses diverse biological activities and has been extensively investigated in various fields, but its impact on rooster reproductive performance and the underlying mechanisms remains poorly understood. The present study investigated the effect of quercetin on reproductive performance of roosters and preliminarily explored its underlying regulatory mechanism. Forty-eight 100-day-old roosters were randomly divided into control group and three quercetin groups (Que_5mg/d, Que_10mg/d, and Que_20mg/d). Daily gavage was conducted continuously for 60 days. Semen quality was evaluated using a sperm analyzer. Then, metabolomics, proteomics, network pharmacology, molecular dynamics simulation, hormone detection, qRT-PCR, and their combination analysis was employed for mechanism validation. The result of semen quality evaluation and testicular tissue morphology observation showed that quercetin can significantly increase the semen collection volume, semen motility (P < 0.05), sperm density was significantly higher in the Que_5mg/d and Que_10mg/d groups than in the control group (P < 0.05), and the diameter of the seminiferous tubules, the height of the seminiferous epithelium of the testes (P < 0.05). Consistently, both testicular metabolomics and hormone detection results indicated that quercetin significantly increased testosterone levels (P < 0.05). Metabolite KEGG enrichment analysis revealed a significant upregulation of the steroid hormone biosynthesis. Proteomics and qRT-PCR assays confirmed that quercetin upregulated the expression of genes such as CYP11A1, CYP17A1, and molecular docking and molecular dynamics simulations further indicate that quercetin has a favorable binding with steroid hormone biosynthesis related protein CYP11A1. These results demonstrates that supplementation with quercetin at a dosage of 10 mg/d can enhances reproductive performance in roosters by targeting steroid hormone biosynthesis-related proteins to promote hormone synthesis.

Breast cancer remains the most common type of cancer affecting women. The estrogen receptor status of a tumor defines the therapeutic approach, which often includes endocrine treatment. Therefore, identifying potential endocrine-disrupting chemicals is of great importance.

Adiponectin and irisin regulate energy homeostasis and interact with peroxisome proliferator-activated receptor coactivator 1α (PGC-1α). However, whether they establish a signal connection via PGC-1α is unclear. In the current study, the expression of irisin was significantly decreased in the skeletal muscle of adiponectin knockout (KO) mice, accompanied by a de crease in APPL1/p38 mitogen-activated protein kinase (MAPK)/PGC-1α. However, adiponectin administration reversed this effect. In vitro, the p38 MAPK/PGC-1α signalling pathway mediated adiponectin-induced FNDC5 expression and irisin release in mouse-derived C2C12 myotube cells. Moreover, obesity caused dysregulation of the adiponectin/APPL1/p38 MAPK/PGC-1α signalling pathway in murine skeletal muscle, ultimately inhibiting irisin synthesis and secretion; meanwhile, prolonged exercise or exogenous recombinant adiponectin intervention activated this pathway in mouse skeletal muscle. This corresponded with an apparent improvement in high-fat diet-induced insulin resistance. The effect of mechanically stretching C2C12 myotube cells was consistent with in vivo findings. Hence, adiponectin upregulates irisin through the APPL1/p38MAPK/PGC-1α signalling pathway in murine skeletal muscle, which may enhance insulin sensitivity.

Iron (Fe) toxicity is a major abiotic stress that compromises crop productivity and quality, yet the underlying molecular mechanisms in medicinal plants like ginseng (Panax ginseng C.A. Meyer) remain poorly elucidated. Here, the core transcription factor PgbHLH149 was identified as being up-regulated by exogenous silicon (Si) and acted as a key regulatory factor in response to Fe toxicity in ginseng. Overexpression of PgbHLH149 in both Arabidopsis and ginseng significantly enhanced Fe stress tolerance through a dual mechanism: 1) modulating elemental homeostasis by reducing Fe accumulation and promoting the uptake of beneficial elements (Ca, Mg, Si); and 2) activating the antioxidant system, thereby increasing enzyme activities (SOD, POD, CAT, APX) and diminishing reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Furthermore, yeast two-hybrid screening revealed that PgbHLH149 interacts with a serine/threonine protein kinase (STPK1) and a fellow transcription factor (bHLH74). And bimolecular fluorescence complementation and co-immunoprecipitation assays confirmed the in vivo interaction between PgbHLH149 and STPK1 in the nucleus. LC-MS/MS analysis further identified phosphorylation of PgbHLH149 at serine-133 by STPK1, indicating post-translational regulation. Under silicon conditions, PgbHLH149 forms a regulatory "STPK1-PgbHLH149-bHLH74" module, which may achieve Fe detoxification by synchronizing elemental homeostasis and antioxidant defense system. Our findings unveiled a novel transcriptional regulatory network for Fe stress tolerance in ginseng, providing crucial molecular targets for breeding rust-resistant varieties and advancing soil remediation strategies in Fe-contaminated soils.

Cadmium (Cd) pollution adversely affects plant growth and development, leading to reductions in crop yields and posing a threat to human health. Selenium (Se) is an essential micronutrient for both humans and animals. Wheat, an important cereal crop, is particularly prone to accumulating Cd in polluted environments. However, there is a paucity of studies examining the mitigation mechanisms of Se on the photosynthetic systems of wheat leaves under Cd stress. In this study, the alleviating effect of Se on Cd toxicity in wheat was investigated. The results showed Se increased wheat biomass by 20 %-50 %, photosynthetic parameters by 26 %-55 %, chlorophyll content by 17 %-29 % and help to keep normal leaf structure under Cd stress. Se upregulated key starch anabolism genes TaAGPS1, TaSUT2, and TaSWEET15 expression level, and thus complemented soluble sugar content by 16 %-21 %, starch content by 15 %-59 % disturbed by Cd stress. Under Cd stress, Se decreased wheat shoot Cd content by 6 %-19 %, and increased shoot Fe, Mn, Zn content by 5-28 %, 23-58 %, 8-32 %, respectively. These results suggest that Se mitigates Cd stress in wheat by limiting Cd translocation to shoots and regulating the expression of key carbon metabolism genes.

Benzo(a)pyrene (B(a)P), a prominent environmental carcinogen, is known to promote lung cancer progression; however, its underlying mechanistic pathways remain poorly defined. Here, we identify the EP300-H2BK5ac epigenetic axis as a key regulator of membrane surface tension and epithelial-mesenchymal transition (EMT) in lung cancer cells under B(a)P exposure. Using A549 and SW900 cells, we demonstrate that B(a)P treatment induces a dose-dependent reduction in membrane tension and promotes EMT, migration, and invasion. Mechanistically, B(a)P downregulates EP300 expression, leading to decreased H2BK5ac acetylation and impaired binding of H2BK5ac to the promoter of the endocytosis-related gene HSPA1A, as revealed by co-immunoprecipitation and ChIP-qPCR. EP300 knockdown mimics these effects, enhancing malignant behaviors, whereas EP300 overexpression restores H2BK5ac levels, increases HSPA1A expression, and suppresses B(a)P-induced phenotypes. Notably, HSPA1A overexpression in EP300-deficient cells partially rescues membrane tension and reverses EMT progression. These findings uncover a previously unrecognized EP300-H2BK5ac-HSPA1A regulatory pathway that links environmental exposure to biomechanical and epigenetic remodeling in lung cancer. Targeting this axis may offer new strategies to mitigate B(a)P-driven metastasis.

This study explored the effects of preharvest L-Phenylalanine (L-Phe) sprays on cuticle development and associated lipid metabolism in muskmelon (Cucumis melo L.) fruit. Spraying 8 mM L-Phe during fruit growth increased cuticle thickness and the accumulation of hydroxy fatty acids, fatty alcohols, alkanes, and triterpenoids. L-Phe enhanced the activities of key enzymes (FAT, LACS, FAR, SQE, OSC) and upregulated genes involved in fatty acid elongation, hydroxylation, alkane and triterpenoid biosynthesis. It also increased ATP-binding cassette (ABCG) transporter and lipid transfer protein (LTP) expression, facilitating transmembrane transport and deposition of wax and cutin monomers. Consequently, treated fruits formed a denser epidermal barrier and improved peel integrity. These findings demonstrate that exogenous L-Phe regulates cutin and wax biosynthesis at both enzymatic and transcriptional levels, providing a theoretical basis for using amino acid treatments to strengthen fruit epidermis and enhance postharvest storability.

Alcohol-related disorders contribute significantly to morbidity, mortality, and economic burdens worldwide. Excessive alcohol consumption affects almost all organs, particularly liver, intestine, and kidney, by generating excessive free radicals during metabolism, which disrupts cellular epigenetic homeostasis and contributes to the disease onset. One of the effective therapeutic strategy for alcohol-induced toxicity involves the use of immunosuppressants and corticosteroids, but with numerous side effects. The exploration of cost-effective, low-toxicity natural products for alcohol-associated liver disease is of growing interest. Moreover, the mechanistic relationship between oxidative stress-induced epigenetic dysregulation and ethanol-induced toxicity remains unexplored. Based on the above concepts, we investigated the effect of gallic acid (GA), a phytochemical known for its potent antioxidant activity against ethanol-induced hepatotoxicity. WRL 68 cells were treated with ethanol and GA under two different conditions: acute (24 h) and chronic (14 d). GA (30 μM) protected cells from oxidative stress by maintaining the levels of SOD, CAT, GSH, and TBARS in the ethanol-treated group. Under acute exposure to ethanol, GA significantly downregulated miR_21_5p, miR_17_5p, HAT, and HDM, and upregulated miR_199a_5p, miR_129_5p, miR_26b_5p, HDACs, and HMTs expression. GA preserved DNA integrity and prevented the cells from undergoing apoptosis by suppressing the expression of apoptotic genes (Cas 3, Cas 9, and Bax). During chronic exposure to ethanol, GA restored cellular homeostasis by maintaining the epigenetic balance of the cells and attenuated EMT progression in WRL 68 cells. Based on our findings, we suggest that GA can act as an antioxidant and protect cells from epigenetic dyshomeostasis during ethanol exposure. However, extensive analyses, such as protein expression profiling and ChIP assays, are required to understand the mechanistic insights of GA in maintaining the epigenetic balance of cells under ethanol toxicity.

Nitrogen (N) plays a crucial role in enhancing plant growth and stress tolerance, but the physiological mechanisms and multi-omics evidence underlying its effect on cadmium (Cd) accumulation and detoxification in woody plants have not been fully understood. In this study, by integrating physiological, transcriptomic, metabolomic, and rhizobacterial analyses, the effects of NH4HCO3-based N fertiliser on 3-month-old poplars subjected to Cd stress were investigated to determine its potential for bioaccumulation and detoxification. Exogenous N significantly enhanced the Cd uptake efficiency and Cd content in whole plants by 93.79 and 160%, respectively, compared to the Cd-only group. N selectively recruited Bacillus, Fictibacillus, and Nitrospira, which are associated with a reduced soil pH, increased Cd bioavailability, and phytohormones (brassinolide and zeatin) biosynthesis, facilitating plant growth and Cd absorption. Concurrently, multi-omics analyses revealed the upregulation of genes involved in reduced glutathione (GSH) and phytohormones biosynthesis, antioxidant defence, and Cd transport and chelation (e.g., PyGCLC, PyGSS, PyDWF, PyIPT, PyAPX, PyCAT, PyNRAMP, PyMT, PyHIPP). Consistently, the accumulation of GSH, key amino acids (cysteine, glutamate, glutamine), phytohormones, flavonoid derivatives (eriodictyol, dihydrokaempferol, glyceollin II), and osmoprotectants (proline, soluble sugars) and the activities of antioxidant enzymes (catalase, superoxide dismutase, peroxidase, ascorbate peroxidase) were enhanced. Thus, Cd-induced reactive oxygen species and lipid peroxidation were reduced, and Cd accumulation and detoxification-related responses were enhanced. These findings suggest that N improves the phytoremediation efficiency of poplar by affecting the rhizosphere environment and Cd bioavailability and by modulating physiological and metabolic processes in plant cells.