Soil salinization severely constrains agricultural production. Sophora alopecuroides L., a salt-tolerant wild legume, is an ideal model for investigating plant salt adaptation mechanisms. However, the dynamic reprogramming of sugar metabolism in its roots under salt stress remains poorly understood. Here, we conducted an integrated transcriptomic and metabolomic analysis of S. alopecuroides roots subjected to 200 mM NaCl over a time course (0, 4, 24, 48, and 72 h). Our results revealed that salt stress triggered a three-phase response: early osmotic stress (0 - 4 h), intermediate adjustment (4 - 48 h), and late ionic stress (48 - 72 h). Integrated multi-omics analysis identified 303 differentially expressed genes (DEGs) and 16 differentially accumulated metabolites (DAMs) from seven core sugar metabolic pathways. Both the DEGs and DAMs were significantly enriched in the starch and sucrose metabolism pathway, and the DEGs exhibited five distinct temporal expression profiles. Coupling analysis of genes and metabolites uncovered a precise "sugar-energy axis" regulatory model: during the early stage, β-amylase (AMY)-mediated starch degradation fueled glycolysis (PFK, GAPDH) for rapid energy production; at the intermediate stage, carbon flux was redirected to the synthesis of osmoprotectants, including sucrose, raffinose, and trehalose (SUS, Rafs, TPS), while the pentose phosphate pathway (PPP) was enhanced to supply NADPH; during the late stage, the TCA cycle (IDH, ACO) was reactivated to restore energy homeostasis, whereas starch synthesis (glgA) was persistently suppressed to conserve carbon sources. This dynamic equilibrium of the "sugar-energy axis" constitutes a central mechanism enabling its efficient salt tolerance. To functionally validate a key node within this axis, we cloned a highly induced enolase gene (SaENO2) from the glycolytic pathway. Heterologous overexpression of SaENO2 significantly enhanced salt tolerance in both yeast (Saccharomyces cerevisiae) and Arabidopsis (Arabidopsis thaliana), confirming its pivotal role in mediating salt adaptation. Our study not only elucidates a dynamic metabolic reprogramming model but also provides a verified genetic resource for improving crop salt tolerance.

Postharvest senescence is a complex biological process that occurs after plant tissues and organs are detached from the mother plant. As an economically important horticultural crop, the senescence of grape berries is closely associated with fruit quality and market value. In this study, integrated transcriptomic and proteomic analyses were conducted to elucidate key metabolic changes during the postharvest senescence of ‘Red Globe’ grape berries. The results showed that genes involved in flavonoid biosynthesis were markedly downregulated, whereas the lignin biosynthetic pathway was activated, competing with the flavonoid pathway for the shared precursor p-coumaroyl-CoA. Correlation analysis identified VvMYB61 and VvNAC29 as candidate core regulators. Yeast one-hybrid and related assays demonstrated that VvMYB61 and VvNAC29 directly bind to the promoter of the lignin biosynthetic gene VvPRX19 and activate its transcription, while VvMYB61 also directly binds to the promoter of the flavonoid biosynthetic gene VvCHS27 and represses its expression. Moreover, both stable and transient transgenic assays revealed that VvMYB61 and VvNAC29 promote lignin accumulation while suppressing flavonoid synthesis. Collectively, these findings establish VvMYB61 and VvNAC29 as key regulators of lignin and flavonoid biosynthesis during grape postharvest senescence, mediating a metabolic reprogramming that redirects carbon flux from flavonoid toward lignin biosynthesis.

Soybean (Glycine max L.) is a major oilseed crop worldwide, and its seed oil quality is largely determined by fatty acid composition. Although the enzymatic framework of plant fatty acid biosynthesis has been extensively characterized, the molecular mechanisms that regulate fatty acid partitioning and seed oil accumulation are not fully understood. In this study, genome-wide association analysis of soybean seed oil content identified GmKASII as a candidate gene underlying natural variation in seed oil accumulation, which was further supported by expression analysis and functional SNP characterization. Genetic manipulation of GmKASII significantly altered soybean seed oil accumulation and fatty acid composition. GmKASII overexpression increased seed oil content and promoted the accumulation of specific C18 fatty acids, including stearic acid (C18:0) and linoleic acid (C18:2), whereas gmkasII knockout reduced seed oil content and resulted in increased palmitic acid (C16:0) and decreased C18:0 levels. Protein-protein interaction assays, including yeast two-hybrid, luciferase complementation, and co-immunoprecipitation analyses, demonstrated that GmKASII physically interacts with acyl-ACP thioesterase GmFATA1B, suggesting a potential functional connection between fatty acid chain elongation and acyl-ACP hydrolysis pathways. Transient expression analysis in tobacco further suggested that co-expression of GmKASII and GmFATA1B influences fatty acid composition in a heterologous system. Collectively, these findings demonstrate that GmKASII plays an important role in regulating plastidial fatty acid flux and seed oil biosynthesis, and reveal a potential regulatory connection between fatty acid elongation and acyl-ACP release pathways in soybean.

A new height locus qPH19.1 was identified, and Glyma.19G206100 was verified as the key gene regulating soybean plant height. Plant height stands as a pivotal component of the plant ideotype and has a substantial influence on crop yield. However, the genetic basis of this trait in soybean plant height remains poorly understood. To identify the genetic determinants of plant height, a BC1F2 segregating population was developed by crossing the super-dwarf soybean line F02 (derived from recombinant inbred lines, RILs) as the paternal parent with ZB (a progenitor of the RIL population) as the maternal parent. Genetic analysis of the BC1F2 population revealed that the ultra-dwarf trait was controlled by a single recessive gene, designated qPH19.1. The candidate gene was initially mapped to chromosome 19 via bulked segregant analysis (BSA-seq) combined with whole-genome sequencing and then fine-mapped to a 53.7-kb region using 2662 BC1F2:3 individuals. Comprehensive sequence analysis, expression profiling, gene annotation, and haplotype analysis identified Glyma.19G206100, which encoded an auxin response factor, as the most probable candidate gene for qPH19.1. Four single-nucleotide polymorphisms (SNPs) in the promoter, coding, and 3′ UTR regions differentiated between the parental lines F02 and ZB, collectively defining five distinct haplotypes. Among them, Hap-2 (ZB type) and Hap-4 (F02 type) predominated in landraces and cultivars, and plants carrying these haplotypes showed significant differences in plant height. These findings provide new perspectives for understanding the genetic mechanisms underlying soybean plant height and offer valuable genetic resources for breeding improved plant architecture.

Cold stress at the booting stage severely disrupts pollen development and drastically reduces grain yield in rice. Uncovering the genetic basis of cold tolerance is essential for breeding resilient varieties. Here, we identified a cold‑sensitive mutant, csb1, from an EMS‑mutagenized population of the cold‑tolerant japonica variety MK1, which exhibits significantly impaired seed‑setting under cold stress. Genetic analysis indicated that the phenotype is controlled by a single recessive nuclear gene. Using MutMap, we mapped the causal locus to a 26.3–27.0 Mb interval on chromosome 8. Among candidate genes, OsPPR7, encoding a PLS‑class pentatricopeptide repeat (PPR) protein, showed strong cold‑induced expression in anthers. A promoter mutation in OsPPR7 was linked to the csb1 phenotype, as confirmed by genetic complementation. CRISPR/Cas9 knockout lines displayed increased cold sensitivity and severe pollen sterility, whereas overexpression enhanced tolerance. Cytological observations revealed that loss of OsPPR7 leads to defective anther development, abnormal pollen nuclei, and failed germination under cold stress. Mechanistically, OsPPR7, localized to mitochondria, regulates cold tolerance by fine‑tuning abscisic acid (ABA) biosynthesis and reactive oxygen species (ROS) homeostasis in young panicles. Haplotype analysis across diverse germplasm identified natural variation in OsPPR7, with the superior cold‑tolerant haplotype Hap_I showing strong selective sweep signals in temperate japonica rice, indicating its role in adaptation to high‑latitude environments. Our study identifies OsPPR7 as a novel positive regulator of reproductive stage cold tolerance and provides a valuable genetic target for improving rice climate resilience.

To adapt to environmental challenges, plants have evolved extensive gene families through duplication events, generating multiple-copy genes that mediate stress responses. However, the function of these duplicated genes in wheat remains unclear. In this study, we identified ten tandemly duplicated ETHYLENE RESPONSE FACTOR 109 (ERF109) genes in wheat, seven of which showed rapid induction under drought treatment. Overexpressing TaERF109A2 resulted in delayed heading date, increased tiller number, reduced plant height and root length, and enhanced drought resilience. Conversely, the CRISPR/Cas9-generated nonuple Taerf109s mutant showed exacerbated growth inhibition under drought stress. RNA-seq and functional analyses indicated that TaMADS56, functioning as a genetic downstream effector of TaERF109A2, modulates wheat tillering, heading date, and drought recovery responses. TaERF109A2 directly binds to the GCC-box motifs in the promoters of TaIPT8-5B/5D, thereby regulating cytokinin (CK) biosynthesis. Moreover, overexpression of TaERF109A2 enhances nicotianamine (NA) accumulation, which in turn confers tolerance to iron toxicity and drought stress via upregulation of nicotianamine synthase (NAS) genes. Our findings have highlighted the critical role of tandemly duplicated genes in the coordination of stress responses and developmental processes in wheat.

GmENDO-like 1, a structurally divergent S1/P1 endonuclease homolog, modulates soybean vegetative-to-reproductive transition; its knockout delays flowering and accelerates leaf senescence. Soybean is a monocarpic crop in which the transition from vegetative to reproductive growth triggers the onset of senescence in vegetative tissues. In this study, we identified a soybean homolog of the S1/P1-type endonuclease gene, GmENDO-like 1, which was significantly upregulated during leaf senescence. Sequence analysis revealed that GmENDO-like 1 has substantial deletions at both the N- and C-termini, resulting in the loss of key residues essential for the active center of canonical S1/P1-type nucleases. Specifically, among the nine conserved amino acids responsible for metal ion coordination, one tryptophan (Trp), two histidines (His), and one aspartic acid (Asp) residue are absent. Although these deletions result in a significant rearrangement of the trinuclear metal-binding center, GmENDO-like 1 remarkably retains intrinsic catalytic activity. Using CRISPR/Cas9-mediated genome editing, we generated two knockout mutant lines of the GmENDO-like 1 gene. Phenotypic analysis revealed a markedly delayed flowering time and an obviously precocious leaf senescence in the GmENDO-like 1 mutant plants. These observations were further corroborated by the altered expression levels of flowering- and senescence-associated marker genes. Both the 100-seed weight and per-plant yield of the mutants were significantly decreased. Collectively, these findings establish GmENDO-like 1 as a functional, evolutionarily divergent nuclease and an essential modulator regulating the vegetative-to-reproductive phase transition in soybean.

Isoflavonoids are widely regarded as phytoalexins and plant estrogens, with applications in plant defense and human healthcare. However, the mechanism of soy isoflavone synthesis remains unclear. In this study, we identified a gene from Glycine max, designated as basic helix-loop-helix 13 (GmbHLH13), which is a member of the bHLH transcription factor family. Overexpression of GmbHLH13 significantly enhanced the accumulation of isoflavonoids in soybean seeds. A combined analysis of the transcriptome and metabolome showed that GmbHLH13 enhanced the expression of multiple genes in the phenylpropanoid metabolism pathway, leading to increased production of downstream metabolites. We established that GmbHLH13 interacted with GmMYB12B2 and GmWD40-7 to form a MYB-bHLH-WD40 (MBW) complex that binded directly to the promoter region of GmCHS7, further increasing GmCHS7 expression. In addition, GmbHLH13 alone or complexed with GmMYB12B2 or GmWD40-7, positively regulated GmCHS7 expression, however, the effect was lower than that of the MBW complex. The findings of this study provide a valuable genetic breeding resource and gene for improving soybean varieties with high isoflavone content.

The auxin/indole-3-acetic acid (Aux/IAA) gene family encodes central regulators of plant development and stress adaptation. Eggplant (Solanum melongena), an economically important vegetable crop, is highly susceptible to abiotic stresses, yet its Aux/IAA family remains uncharacterized. This study aimed to systematically characterize the Aux/IAA gene family in eggplant and to explore its potential roles in development and abiotic stress responses using a genome-wide approach. Here, 35 SmIAA genes were identified through comprehensive bioinformatic analyses, including phylogenetic classification, synteny analysis, protein-protein interaction prediction, and qRT-PCR validation. Phylogenetic analysis classified these genes into Clades A and B, encompassing nine subgroups, with subgroup B4 showing lineage-specific expansion and encoding non-canonical Aux/IAA proteins. Expression profiling revealed that SmIAA18 and SmIAA33 were strongly responsive to salt stress, whereas SmIAA1/2/8 were preferentially induced by drought stress. Furthermore, SmIAA8 and SmIAA33 exhibited contrasting responses to IAA treatment, characterized by delayed induction and rapid repression, respectively. This study presents the first genome-wide analysis of the Aux/IAA family in eggplant, elucidating its roles in development and stress adaptation, and provides valuable genetic resources for the molecular breeding of stress-tolerant varieties.

Plant biomass is an important agronomic trait that has been subjected to intense human selection for yield improvement. The underlying mechanism regulating biomass formation is currently gaining increasing attention, but it remains unexplored. In this study, we isolated a cucumber (Cucumis sativus L.) minicuke mutant with remarkably reduced biomass. The causative gene was identified as CsNMT1, a homologue of the Arabidopsis thaliana N-myristoyltransferase1. Our clustered regularly interspaced shot palindromic repeat-based genome editing confirmed the key role of CsNMT1 in biomass regulation. Multi-omics analyses integrating metabolomic and transcriptomic analyses revealed the suppression of a very early step of lignin biosynthesis and the corresponding down-regulation of genes involved in lignin biosynthesis in the minicikue mutant, suggesting an unexpected pathway for regulating biomass accumulation through lignin sink strength. Our findings demonstrate the function of NMT1 in regulating plant biomass and its potential application value for biomass improvement in cucurbits.

Theanine, a unique non-protein amino acid, is specifically accumulated in tea plants during winter. This study explored the theanine accumulation patterns in ‘Longjing 43’ and ‘Huangjinya’ under different N supply conditions and analyzed the expression of genes involved in theanine biosynthesis during winter dormancy. We found that the two tea plant cultivars shared similar theanine accumulation patterns in winter. After 30 d of cultivation with various N forms and N deficiency, the theanine content in the tissues of both cultivars was highest in the control group, followed by NH4+ treatment. Furthermore, we noted that root growth of tea plants was inhibited to varying degrees under different N sources and N-deficient conditions. Gene expression analysis revealed that both N forms can induce the transcription of key genes, including CsADC, CsALT, CsCuAO, CsGDH2, CsPAO, CsNiR, CsNR, and CsTS1 in ‘Longjing 43’ and ‘Huangjinya’. The expression of these genes was strongly correlated with theanine levels under the N treatments. The winter theanine accumulation was finely tuned by the interplay of multiple related genes, with expression levels varying across different cultivars and tissues.

Carotenoids play a significant role in the growth, development, color, and aroma quality of tea plants. The molecular mechanism underlying carotenoid metabolism in tea plants remain to be elucidated. In this study, we determined the carotenoid contents in three tea cultivars (‘Suchazao’, ‘Huangjinya’, and ‘Zhongbai 4’) and conducted transcriptome sequencing on the new shoots and mature leaves of these cultivars. Our results indicated that lutein was the predominant carotenoid in ‘Suchazao’ and ‘Zhongbai 4’, whereas β-carotene was the predominant carotenoid in ‘Huangjinya’. The mature leaves of all three tea cultivars contained higher carotenoids levels compared to the new shoots. In the transcriptome analysis, we identified 24 and 20 key DEGs involved in carotenoid biosynthesis and degradation, respectively. Expression analysis and correlation analysis indicated that CsPSY, CsPDS, CsZDS, CsLCYE, CsLCYB, CsBCH, CsCYP97A3, CsZEP, CsOR, CsCCD1.2, and CsCCD4 play crucial roles in the carotenoid metabolism in tea plants. Furthermore, several transcription factors, including CsMYB59-LOC114278066 and CsNAC56-LOC114260089, were identified in pairwise comparisons, implying their potential role in carotenoid accumulation. These results elucidated carotenoid accumulation patterns in new shoots and mature leaves of three tea cultivars with different leaf colors. It also provided insights into the molecular mechanism that regulate carotenoid accumulation in tea plants.

Response regulator proteins (RRs) are integral components of two-component regulatory systems and play critical roles in cytokinin signaling, regulation of plant growth and development, and responses to biotic and abiotic stresses. While numerous RR families have been identified, comprehensive characterization and functional studies of RR genes in eggplant have not been reported. In this study, we conducted a genome-wide identification and analysis of RR genes in eggplant. Through Blastp and HMM methods, a total of 32 RRs were identified. Phylogenetic analysis classified all RRs into three categories: type-A, type-B RRs, and PRRs (Pseudo-RRs), while no type-C genes were detected. Gene structure and motif analysis demonstrated similarities within each type. Gene duplication and tandem repeats suggested these mechanisms might have facilitated the expansion of the RR gene family in the eggplant genome. Synteny analysis uncovered 18 syntenic blocks between eggplant and Arabidopsis and 33 between eggplant and tomato. Promoter analysis indicated their potential roles in hormone signaling and stress responses. Tissue expression data showed that 12 genes had no or undetectable expression across 17 tested tissues, while others exhibited significant tissue specificity, with most genes showing higher expression in roots. Dynamic expression of 11 selected RR genes in response to salt, drought stress, and IAA hormone treatment in eggplant seedlings revealed that most genes responded to all three treatments. Notably, SmRR9 exhibited the most profound response to salt stress, SmRR1 and SmRR9 to drought stress, and SmRR5 and SmRR6 to IAA treatment. These four genes were proposed as key candidates for future studies on RR gene functions in abiotic stress responses and hormone signaling pathways. The findings of this study provide a foundation for future research on the functional roles of SmRRs in abiotic stress responses and hormone signaling pathways in eggplant, serving as a guide for improving stress tolerance in eggplant.

Daylily is a unique cash crop in China which uses the unopened flower buds as food organs. Fresh daylily easily deteriorates and dried daylily is the main supply form in the market at present. The main goal of this work is to determine dried daylily water rehydration properties and sugar, lignin, cellulose, carotenoid, flavonoid and polyphenol retention properties under different temperatures and time periods. In this study, daylily was soaked at room temperature (25 °C), 50 °C and 70 °C for different durations. The results showed that after rehydration, the brightness index of daylily increased, while the redness and yellowness value decreased. The higher the water temperature, the faster the water absorption expansion rate and the higher the rehydration rate of the dried daylily, but the higher water temperature can cause the destruction of the microstructure of the daylily. The soluble sugars of dried daylily were easily lost in the rehydration process, the contents of lignin, cellulose and carotenoid were relatively stable. The contents of polyphenols and flavonoids decreased significantly with the increase of rehydration time. The rehydration of dried daylily can be carried out at room temperature, and it is recommended that the rehydration time take 0.5 h.

Biological nitrogen fixation (BNF) is the most cost-effective and environmentally benign method for nitrogen fertilization. Isoflavones are important signaling factors for BNF in leguminous plants. Whether chalcone isomerase (CHI), the key enzyme gene in the flavonoid synthesis pathway, contributes to soybean (Glycine max) nodulation has not yet been fully clarified. In the present study, we identified the functions of three types of GmCHI for BNF using a hairy root system. The results showed that GmCHI1A and GmCHI1B1 positively increased nodulation while GmCHI1B2 did not, with the GmCHI1A gene having a greater effect than GmCHI1B1. Meanwhile, the daidzein and genistein contents were significantly increased in composite plants overexpressing GmCHI1A and reduced in composite plants, thus interfering with GmCHI1A. However, overexpression of GmCHI1B1 significantly increased the content of glycitein but not daidzein, genistein content implied that homologous genes exhibit functional differentiation. These results provide a reference for subsequent studies on improving nitrogen fixation in soybeans and providing functional genes for the improvement of new varieties.

Prefertilization hybridization barriers are the main causes of intersubgeneric hybridization challenges in water lily. However, the mechanism underlying low compatibility between pollen and stigma of water lily remains unclear. This study demonstrates that CBL-interacting protein kinase 6 (CIPK6) responded to the signaling exchange between incompatible pollen and stigma through interactions with SNF1-related kinase 1 (SnRK1) and promotes the accumulation of SnRK1 protein. Activated SnRK1 interacted with 9-cis-epoxycarotenoid dioxygenase 2 (NCED2) to promote its degradation, thereby inhibiting abscisic acid (ABA) synthesis. A decrease in ABA content in the stigma impaired the ABA-mediated removal of reactive oxygen species (ROS), ultimately resulting in the rejection of the incompatible pollen by the stigma. Our results highlight the essential role of the NpCIPK6-NpSnRK1-NpNCED2 module in conferring intersubgeneric hybridization barriers in water lily by interfering with ABA synthesis and promoting ROS accumulation. This study offers valuable mechanistic insights into cellular signaling and reproductive barriers in water lily as well as across other biological contexts.

Soybean isoflavones, natural phytoestrogens within the flavonoid family, exhibit diverse physiological benefits such as anticancer, antioxidant, and cardioprotective properties. Yet, the underlying biosynthetic pathways remain unclear. Research is required to get better knowledge of soybean isoflavone production and its potential uses. Our work thoroughly examined the R2R3-MYB subclass in soybean and discovered a new MYB transcription factor, GmMYB3a, which shares significant similarities with Arabidopsis MYB genes and regulates isoflavone biosynthesis. Our study reveals that GmMYB3a localizes to the nucleus and membrane, concurs with its potential involvement in the biosynthesis of isoflavones. Our analysis also indicated a synergistic expression pattern between GmMYB3a and seed development, thereby creating the hypothesis that it has a critical role in the regulation of isoflavone synthesis. Transgenic experiments further demonstrated that GmMYB3a positively regulates isoflavone biosynthesis and leads to its overexpression. GmMYB3a has been implicated in abiotic stress responses, affecting soybean stress tolerance. RNA sequencing analysis revealed that GmMYB3a regulates downstream genes involved in isoflavone, flavonoid, and phenylalanine metabolism, especially the key chalcone synthase genes, CHS7 and CHS8. Moreover, GmMYB3a was shown to be tightly associated with GmCHS7 and GmCHS8 expressions, potentially regulating them directly. Yeast two-hybrid screening identified GmMYB3a interacting proteins crucial for the synthesis of physiologically active substances and abiotic stress responses. Our results increase knowledge of the regulatory mechanisms of GmMYB3a and establish a molecular network involving GmMYB3a, GmCHS7, and GmCHS8, thereby offering novel strategies for improving soybean quality and stress-tolerant breeding.

Chromium (Cr) is a toxic heavy metal that affects the food chain and poses a severe threat to food safety. Nonetheless, the N6-methyladenosine (m6A) transcriptomic regulation mechanisms of Cr tolerance genes in rice are not well understood. This study found that rice roots exhibit competitive and synergistic interactions with trace elements under Cr stress. Through a comprehensive transcriptome analysis of m6A methylation profiles under Cr stress, differentially methylated genes (DMGs) closely related to the plasma membrane, oxidoreductase activity, and protein phosphorylation were identified. A significant number of differentially expressed genes (DEGs) associated with heavy metal transporter domains, metalloproteases, metal ion transporters, and other cation transporters were strongly induced by Cr. Additionally, OsHMT9.1 exhibited extensive hypomethylation and up-regulation in Cr-exposed roots and was confirmed to be a regulatory factor for Cr tolerance. Enhanced plant resistance to Cr in oshmt9.1 was accompanied by increased levels of P, K, S, and Ca and decreased levels of Mn and Cu. These results suggest that knocking out OsHMT9.1 can promote Cr detoxification in rice by modulating the balance between Cr and other trace elements. These findings provide new insights into the molecular regulation and stress response of rice under Cr stress through transcriptome m6A methylation patterns.

As there are no effective treatments for advanced prostate cancer, exploring new therapies is crucial. BI6727(Volasertib), a PLK1 inhibitor, shows great promise as an anti-cancer drug. However, despite advancing to phase II and III trials in other cancers, BI6727 has shown limited anti-tumor activity in prostate cancer, making it crucial to investigate the underlying reasons for this discrepancy. In this study, we found that the status of p53 affects the sensitivity of prostate cancer cells to BI6727. Prostate cancer cells PC3 (long-term loss of p53 expression), DU145 (expressing mutant-type p53) and LNCaP (expressing wild-type p53) were treated with BI6727, respectively. It was found that PC3 cells were more sensitive to BI6727 when wild-type p53 was introduced into these cancer cells; while apoptosis induced by BI6727 was reduced after knockdown of p53 in LNCaP cells. In additional, in DU145 cells, the presence of points mutation in p53 exerted a dominant negative effect, attenuating BI6727-induced apoptosis. Further analysis revealed that missense mutations in the P53 gene are widespread in prostate cancer patients. Mechanistically, BI6727 reduces the degradation of Topors, thereby increasing the stability of p53 by reducing its ubiquitination. This ultimately influences the sensitivity of prostate cancer cells with different p53 statuses to BI6727.In summary, this study identifies p53 as a key factor limiting the clinical efficacy of BI6727 in prostate cancer cells.