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Background: Polyamines metabolism is closely related to tumor development and progression, as well as tumor microenvironment (TME). In this study, we focused on exploring whether polyamines metabolism-associated genes would provide prognosis and immunotherapy response prediction in lung adenocarcinoma (LUAD). Methods: The expression profile data of polyamines metabolism-associated genes were acquired from the Cancer Genome Atlas (TCGA) database. Utilizing the least absolute shrinkage and selection operator (LASSO) algorithm, we created a risk score model according to polyamines metabolism-associated gene signatures. Meanwhile, an independent cohort (GSE72094) was employed to validate this model. Through the univariate and multivariate Cox regression analyses, the independent prognostic factors were identified. Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect their expression in LUAD cells. By consensus clustering analysis, polyamines metabolism-associated subgroups were determined in LUAD patients, with differential gene expression, prognosis, and immune characteristics analyses explored. Results: A total of 59 polyamines metabolism genes were collected for this study, of which 14 genes were identified for the construction of risk score model using LASSO method. High- and low- risk groups of LUAD patients in TCGA cohort were distinguished via this model, and high-risk group presented dismal clinical outcomes. The same prognostic prediction of this model had been also validated in GSE72094 cohort. Meanwhile, three independent prognostic factors (PSMC6, SMOX, SMS) were determined for constructing the nomogram, and they were all upregulated in LUAD cells. In addition, two distinct subgroups (C1 and C2) were identified in LUAD patients. Comparing the two subgroups, 291 differentially expressed genes (DEGs) were acquired, mainly enriching in organelle fission, nuclear division, and cell cycle. Comparing to C1 subgroup, the patients in C2 subgroup had favorable clinical outcomes, increased immune cells infiltration, and effective immunotherapy response. Conclusion: This study identified polyamines metabolism-associated gene signatures for predicting the patients' survival, and they were also linked to immune cells infiltration and immunotherapy response in LUAD patients. [ABSTRACT FROM AUTHOR]

The vanadium (V) toxicity predominantly is the primary limitation in restraining pepper growth. The silicon (Si) in pepper plants induced the transcript level of the polyamines metabolism pathway genes, including the arginase (CbARG), ornithine decarboxylase (CbODC), arginine decarboxylase (CbADC), N-carbamoylputrescine amidase (CbNCA), Spermidine synthase (CbSPDS), copper binding diamine oxidase (CbCuAO) to overcome the V toxicity. The polyamines, including the Spm, Spd, and Put, induced with Si about 41.37 %, 33.12 %, and 27.90 %, respectively, in V stress. Moreover, the Si application decline in the leaf and root V contents, which was around 49.5 % and 40.74 %, respectively, then the V stress plants. The soluble protein, proline, and Si level in root/leaf with Si treatment significantly induced around 55.55/50.22 %, 42.85/55.35 %, and 49.92/85.29 %, respectively, as compared to the V stress. Si also heightened the nitrate reductase (NR), phosphoenolpyruvate carboxylase (PEPC), and malate dehydrogenase (MDH) levels. Our study revealed that Si maintained the PSII integrity and induced PSII efficiency genes. Si preserves the membrane stability, as evidenced by less accumulation in EL, H 2 O 2, and MDA levels. The Si also induces the AsA-GSH to eliminate the reactive oxygen species (ROS) in the pepper plants. In summary, our research elucidated that Si addition improved pepper plants' tolerance to V toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

By using Skeletonema dohrnii as the experimental algal species, we investigated how silicate concentration impacts the polyamine metabolism of diatoms in our experiment. Three different silicate concentrations were set for cultivation, and Skeletonema dohrnii at the exponential growth phase was selected to analyze basic physiological parameters, polyamine content, and Polyamine oxidase (PAO) gene expression under varying silicate concentrations. Results showed that low silicate concentrations led to reduced growth rate and polyamine content, with down-regulation of PAO gene expression. Conversely, high silicate concentrations did not significantly increase growth rate but did increase polyamine content and up-regulate the PAO gene. These findings suggested that changes in silicate concentration impact the growth rate and polyamine content of Skeletonema dohrnii, with the PAO gene potentially playing a role in regulating the algal response to silicate concentration variations. This study provides a foundation for further exploration of the PAO gene function in Skeletonema dohrnii., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The intestinal epithelium is a rapidly self-renewing tissue; the rapid turnover prevents the invasion of pathogens and harmful components from the intestinal lumen, preventing inflammation and infectious diseases. Intestinal epithelial barrier function depends on the epithelial cell proliferation and junctions, as well as the state of the immune system in the lamina propria. Polyamines, particularly putrescine, spermidine, and spermine, are essential for many cell functions and play a crucial role in mammalian cellular homeostasis, such as that of cell growth, proliferation, differentiation, and maintenance, through multiple biological processes, including translation, transcription, and autophagy. Although the vital role of polyamines in normal intestinal epithelial cell growth and barrier function has been known since the 1980s, recent studies have provided new insights into this topic at the molecular level, such as eukaryotic initiation factor-5A hypusination and autophagy, with rapid advances in polyamine biology in normal cells using biological technologies. This review summarizes recent advances in our understanding of the role of polyamines in regulating normal, non-cancerous, intestinal epithelial barrier function, with a particular focus on intestinal epithelial renewal, cell junctions, and immune cell differentiation in the lamina propria., Competing Interests: Declarations. Ethics approval: No human and animal experiment data were generated for this review article. Competing Interests: The authors declare no competing interests., (© 2025. The Author(s).)

Biological polyamines, such as spermine, spermidine, and putrescine, are abundant intracellular compounds mostly bound to nucleic acids. Due to their nucleophilic nature, polyamines easily react with apurinic/apyrimidinic (AP) sites, DNA lesions that are constantly formed in DNA by spontaneous base loss and as intermediates of base excision repair. A covalent intermediate is formed, promoting DNA strand cleavage at the AP site, and is later hydrolyzed regenerating the polyamine. Here we have investigated formation of AP site adducts with spermine and spermidine using sodium borohydride trapping technique and shown that they could persist in DNA for long enough to possibly interfere with cell's replication and transcription machinery. We demonstrate that both adducts placed internally into DNA are strongly blocking for DNA polymerases (Klenow fragment, phage RB69 polymerase, human polymerases β and κ) and direct dAMP incorporation in the rare bypass events. The internal AP site adducts with polyamines can be repaired, albeit rather slowly, by Escherichia coli endonuclease IV and yeast Apn1 but not by human AP endonuclease APE1 or E. coli exonuclease III, whereas the 3'-terminal adducts are substrates for the phosphodiesterase activities of all these AP endonucleases.

Altered human aldo-keto reductase family 1 member C3 (AKR1C3) expression has been associated with poor prognosis in diverse cancers, ferroptosis resistance, and metabolic diseases. Despite its clinical significance, the endogenous biochemical roles of AKR1C3 remain incompletely defined. Using untargeted metabolomics, we identified a major transformation mediated by AKR1C3, in which a spermine oxidation product "sperminal" is reduced to "sperminol." Sperminal causes DNA damage and activates the DNA double-strand break response, whereas sperminol induces autophagy in vitro. AKR1C3 also pulls down acyl-pyrones and pyrone-211 inhibits AKR1C3 activity. Through G protein-coupled receptor ligand screening, we determined that pyrone-211 is also a potent agonist of the semi-orphan receptor GPR84. Strikingly, mammalian fatty acid synthase produces acyl-pyrones in vitro, and this production is modulated by NADPH. Taken together, our studies support a regulatory role of AKR1C3 in an expanded polyamine pathway and a model linking fatty acid synthesis and NADPH levels to GPR84 signaling., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Wheat germ is one of the richest natural sources of polyamines, especially spermidine. Cell proliferation property of polyamines has given them inductive effects in the reduction of a variety of chronic diseases and fertility enhancement. Preparing a polyamine-rich extract powder from wheat germ for use in supplements is the aim of the present study. For the first time, the effects of three independent variables of clean-up replicate (A), extraction time (B), and solid-to-liquid ratio (C) on the response of total spermidine content (Y) were investigated using a central composite design optimizing polyamine enrichment. The optimal extraction conditions were 7 h, 3 clean-up replicates, and 1:4 solid to liquid ratio. This is the first production report of spermidine-enriched powder for encapsulation purposes. To obtain an acceptable rheological property, the polyamine-enriched extract was spray dried together with a selected group of excipients, among which glucose was evidenced as the best choice based on encapsulation properties., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare. All co-authors have seen and agree with the contents of manuscript and there is no financial interest to report. We certify that the submission is original work and is not under review at any other publication., (Copyright © 2024. Published by Elsevier Ltd.)

Bacterial contamination is an inevitable issue during the processing of semen preservation in pigs. As a prototypical endotoxin from Gram-negative bacteria in semen, lipopolysaccharide (LPS) undermines sperm function during liquid preservation. Spermine and spermidine could protect cells against LPS-induced injury, and the content of spermine and spermidine in seminal plasma is positively correlated with sperm quality. Thus, the present study aimed to clarify whether addition of spermine or spermidine is beneficial to porcine semen preservation and able to prevent LPS-induced sperm damage. The supplementation of spermine and spermidine in the diluent resulted in higher sperm motility, viability, acrosome integrity, and mitochondrial membrane potential (ΔΨm) after preservation in vitro at 17 °C for 7 d (P < 0.05). LPS-induced sperm quality deterioration, ΔΨm decline, cellular adenosine-triphosphate depletion, mitochondrial ultrastructure abnormality, mitochondrial permeability transition pore opening, phosphatidylserine (PS) translocation, and caspase-3 activation (P < 0.05). Interestingly, spermine and spermidine alleviated the LPS-induced changes of the aforementioned parameters and mitigated the decrease in the microtubule-associated protein light chain 3-II (LC3-II) to LC3-I ratio. Meanwhile, the α and β subunits of casein kinase 2 (CK2) were detected at the connecting piece and the tail. Significantly, addition of 4,5,6,7-tetrabromobenzotriazole, a specific CK2 inhibitor, counteracted the beneficial effects of spermine and spermidine on sperm quality, mitochondrial activity, and apoptosis. Together, these results suggest that spermine and spermidine improve sperm quality and the efficiency of liquid preservation of porcine semen. Furthermore, spermine and spermidine alleviate LPS-induced sperm mitochondrial dysfunction and apoptosis in a CK2-dependent manner., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Trimethylamine monooxygenase (Tmm, EC-1.14.13.148) belongs to the family of flavin-containing monooxygenases that oxidize trimethylamine into trimethylamine-N-oxide (TMAO). Conventional methods for assaying Tmm are accurate over a narrow range of substrate/product concentrations. Here we report a TMAO-specific enzymatic assay for Tmm using polyallylamine hydrochloride (PAHCl)-capped MnO 2 nanoparticles (PAHCl@MnO 2 ). We achieved TMAO specificity using iodoacetonitrile to remove interfering trimethylamine. The change in the concentration of TMAO is measured by observing the difference in the absorbance of 3,3',5,5'-tetramethylbenzidine (TMB) at 650 nm. The assay is tolerant to several interfering metal ions and other compounds. This method is more accessible and reliable than currently known methods. The limit of detection (LOD) and limit of quantitation (LOQ) are 1 μM and 10 μM, respectively, for direct TMAO measurement., (© 2023 Wiley Periodicals LLC.)

A partly infected plant becomes more resistant to subsequent infections by developing systemic acquired resistance (SAR). Primary infected tissues produce signals that travel to systemic tissues for SAR-associated priming of defense-related genes. The mechanism through which mobile signals contribute to long-lasting infection memory is mostly unknown. RSI1/FLD, a putative histone demethylase, is required for developing SAR. Here, we report that two other FLD homologs, LSD1-LIKE2 (LDL2) and POLYAMINE OXIDASE 5 (PAO5), are required for SAR development. The mutants of LDL2 and PAO5 are not defective in local resistance but are specifically impaired for SAR. The mutants are defective in salicylic acid accumulation and priming of defence-related genes such as PR1, FMO1, and SnRK2.8. LDL2 and PAO5 are expressed in systemic tissues upon SAR induction by pathogens or SAR mobile signal azelaic acid. The ldl2 and pao5 mutants generate SAR mobile signals like wild-type (WT) plants but fail to respond to the signal at the systemic leaves. Both LDL2 and PAO5 proteins contain polyamine oxidase (PAO) domains, suggesting their involvement in polyamine metabolism. Exogenous applications of polyamines such as spermine and spermidine activate SAR in WT and rescue SAR defects of ldl2 and pao5 plants. Inhibition of polyamine biosynthetic gene arginine decarboxylase blocks SAR development. Results altogether demonstrate specific non-redundant roles of LDL2 and PAO5 in SAR development with their possible involvement in polyamine metabolism., (© 2025 Scandinavian Plant Physiology Society.)

This study aims to elucidate a novel mechanism for elevating the pH within the calicoblastic extracellular calcifying medium (pH ECM ) of corals and demonstrate the potential contribution of calcifying organisms to CO 2 sequestration. Departing from traditional models that attribute the increase in pH ECM primarily to H + expulsion via Ca 2+ -ATPase, we emphasize the significant role of polyamines. These ubiquitous biogenic amines conveyed by calicoblastic cells through polyamine transporters demonstrate a remarkable affinity for CO 2 . Their ability to form stable carbamate complexes is pivotal in facilitating carbonate ion transport, which is crucial for pH regulation and skeletal structure formation. In this study, a polyamine transporter inhibitor and a polyamine biosynthesis inhibitor in conjunction with the pH-sensitive probe 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) were employed to monitor pH variations. Furthermore, FM1-43FX dye was utilized to delineate the extracellular calcifying medium (ECM), whereas calcein was applied to visualize paracellular gaps and ECM. These methodologies provide profound insights into the intricate structural and functional dynamics of coral spats calcification. Findings suggest a potential reconsideration of established models of marine calcification and highlight the necessity to reassess the role of marine calcifying organisms in the carbon cycle, particularly their influence on CO 2 fluxes.

The deregulation of amino acid and polyamine metabolism is a hallmark of malignancy that regulates cancer cell proliferation, angiogenesis, and invasion. A sensitive mass spectrometry method was developed to simultaneously quantify 10 cancer-associated metabolites in pleural effusion cells for the diagnosis of malignancy and to complement conventional pleural cytology. Analytes were detected by high-performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) using C8-reversed-phase HPLC for separation and sequential window acquisition of all theoretical fragment ion spectra (SWATH) acquisition for obtaining high-resolution quantitative MS/MS chromatograms. This method was validated and applied to pleural effusion cells from patients with lung adenocarcinoma (LUAD, n = 48) and those from benign controls (n = 23). The range of the above metabolites was 2-200 ng/mL for proline, aspartate, ornithine, creatine, glutamine, glutamate, arginine, citrulline, and spermine and 10-1000 ng/mL for putrescine. The intra-assay and inter-assay coefficient of variation was below 13.70 % for all analytes. The joint detection of these metabolites in pleural effusion cells achieved a clinical sensitivity of 75.0 % and specificity of 95.7 % differentiating LUAD patients from benign controls. This assay enabled the detection of 10 cancer-associated metabolites in pleural effusion cells, and the increased concentration of these metabolites was correlated with the presence of LUAD., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Tingting Wang reports financial support was provided by National Natural Science Foundation of China. Tingting Wang reports financial support was provided by the Jilin Province Natural Science Foundation Project. Tingting Wang reports financial support was provided by the Science and Technology Research Project from the Education Department of Jilin Province. Jing Huang reports financial support was provided by Science and Technology Innovation Platform of Jilin Province. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Placental insufficiency often correlates with fetal growth restriction (FGR), a condition that has both short- and long-term effects on the health of the newborn. In our study, we analyzed placental tissue from infants with FGR and from infants classified as small for gestational age (SGA) or appropriate for gestational age (AGA), performing comprehensive analyses that included transcriptomics and metabolomics. By examining villus tissue biopsies and 3D trophoblast organoids, we identified significant metabolic changes in placentas associated with FGR. These changes include adaptations to reduced oxygen levels and modifications in arginine metabolism, particularly within the polyamine and creatine phosphate synthesis pathways. Specifically, we found that placentas with FGR utilize arginine to produce phosphocreatine, a crucial energy reservoir for ATP production that is essential for maintaining trophoblast function. In addition, we found polyamine insufficiency in FGR placentas due to increased SAT1 expression. SAT1 facilitates the acetylation and subsequent elimination of spermine and spermidine from trophoblasts, resulting in a deficit of polyamines that cannot be compensated by arginine or polyamine supplementation alone, unless SAT1 expression is suppressed. Our study contributes significantly to the understanding of metabolic adaptations associated with placental dysfunction and provides valuable insights into potential therapeutic opportunities for the future., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Leishmania donovani ( Ld ) promastigotes secrete exosomes that are crucial in host-pathogen interactions and intercellular communication by carrying parasite-specific molecules. Although the composition of cargos in Leishmania exosomes is known, the effects of the unique metabolic repertoire on immunometabolism rewiring of macrophage polarization are poorly understood. Interestingly, we found the enrichment of polyamines (PAs) such as spermidine and putrescine in the Ld -exosomes. Herein, we investigate the critical polycationic molecules and their crucial role in parasite survival. Our study shows that PA inhibition or depletion significantly impairs parasite growth and fitness, particularly in drug-resistant strains. Furthermore, we aimed to elucidate the impact of PAs-enriched Ld -exosomes on host macrophages. The data demonstrated that macrophages efficiently internalized these exosomes, leading to heightened phagocytic activity and infectivity. In addition, internalized Ld -exosomes induced M2 macrophage polarization characterized by elevated Arginase-1 expression and activity. The increased expression of the solute carrier gene (SLC3A2) and elevated intracellular spermidine levels suggest that Ld -exosomes contribute to the host PAs pool and create an anti-inflammatory milieu. These findings highlight the essential role of PAs-enriched Ld -exosomes in parasite survival and establishing a pro-parasitic environment in the host macrophage.

Sweet potato ( Ipomoea batatas ) serves as a significant food and economic crop worldwide. However, its production and safety are jeopardized by black rot, a disease caused by Ceratocystis fimbriata . Although polyamines (PAs) are common biological growth factors, their function in the storage of fruits and vegetables remains poorly understood. This study examines the physiological roles of both exogenous and endogenous PAs in C. fimbriata , particularly their metabolism via gene knockout techniques. Additionally, we assessed how exogenous PAs affect sweet potato storage resistance. Our findings reveal that PAs are crucial in managing oxidative and cell wall stress in C. fimbriata . At high concentrations, PAs displayed cytotoxic effects through the upregulation of nitric oxide synthase ( TAH18 ). Furthermore, exogenous PAs significantly enhanced the defense mechanisms of sweet potatoes during storage. The concurrent use of perillaldehyde (PAE), a natural antibacterial compound, additionally decreased the incidence of black rot in sweet potatoes. This study provides a novel strategy and theoretical basis for the prevention and control of fungal diseases in stored fruits and vegetables.

The polyamines putrescine, spermidine, and spermine are polycations ubiquitously present in cells, where they exert pleiotropic functions in cellular mechanisms like proliferation, protein synthesis (through the hypusination of the transcription factor EIF5a), redox balance, autophagy, and different forms of cell death [...].

Polyamines act as protective compounds directly protecting plants from stress-related damage, while also acting as signaling molecules to participate in serious abiotic stresses. However, the molecular mechanisms underlying these effects are poorly understood. Here, we utilized metabolome genome-wide association study to investigate the polyamine content of wild and cultivated tomato accessions, and we discovered a new gene cluster that drove polyamine content during tomato domestication. The gene cluster contains two polyphenol oxidases (SlPPOE and SlPPOF), two BAHD acyltransferases (SlAT4 and SlAT5), a coumaroyl-CoA ligase (Sl4CL6), and a polyamine uptake transporter (SlPUT3). SlPUT3 mediates polyamine uptake and transport, while the five other genes are involved in polyamine modification. Further salt tolerance assays demonstrated that SlPPOE, SlPPOF, and SlAT5 overexpression lines showed greater phenolamide accumulation and salt tolerance as compared with wild-type (WT). Meanwhile, the exogenous application of Spm to SlPUT3-OE lines displayed salt tolerance compared with WT, while having the opposite effect in slput3 lines, confirms that the polyamine and phenolamide can play a protective role by alleviating cell damage. SlPUT3 interacted with SlPIP2;4, a H 2 O 2 transport protein, to maintain H 2 O 2 homeostasis. Polyamine-derived H 2 O 2 linked Spm to stress responses, suggesting that Spm signaling activates stress response pathways. Collectively, our finding reveals that the H 2 O 2 -polyamine-phenolamide module coordinately enhanced tomato salt stress tolerance and provide a foundation for tomato stress-resistance breeding., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

GABA is able to increase resistance to biotic and abiotic stresses in fresh-cut fruits and vegetables. Therefore, the objective of this research was to explore the potential regulatory mechanisms of γ-aminobutyric acid (GABA) accumulation in fresh-cut stem lettuce following GABA treatment. The evidence showed that exogenous GABA stimulated the GABA shunt by elevating glutamate levels, the activities of GABA transaminase (GABA-T) and glutamate decarboxylase (GAD). Similarly, GABA stimulated polyamine metabolism by increasing the activities of 4-amino aldehyde dehydrogenase (AMADH), polyamine oxidase (PAO) and diamine oxidase (DAO), as well as elevating free polyamines, arginine and ornithine levels. Subsequently, GABA application up-regulated the expression of GABA shunt genes and polyamine metabolism genes. Additionally, GABA treatment resulted in the down-regulation of LsMYB44 and LsWRKY12 expressions. Notably, LsMYB44 bound to MYB binding sites in the LsGAD, LsGABAT1, LsADC1, LsPAO2, LsALDH7B4 promoters and repressed transcription of these genes. The interaction between LsMYB44 and LsWRKY12 was associated with the transcriptional repression of polyamine metabolism and GABA shunt genes by LsMYB44. In conclusion, LsMYB44 and LsWRKY12 downregulated the transcription of key genes of GABA shunt and polyamine metabolism in fresh-cut lettuce. This downregulation, however, was alleviated by the application of GABA, thereby promoting endogenous GABA accumulation., Competing Interests: Declaration of competing interest, (Copyright © 2024 Elsevier B.V. All rights reserved.)

The extensive development in light-emitting diodes (LEDs) in recent years provides an opportunity to positively influence plant growth and biomass accumulation and to optimize biochemical composition and nutritional quality. This study aimed to assess how different light spectra affect the growth, photosynthesis and biochemical properties of Eruca sativa. Therefore two LED lighting modes - red:blue (RB, 1:1) and red:green:blue (RGB, 2:1:2) were compared to the conventional white light fluorescent tubes (WL). Plant biomass, photosynthetic performance, several antioxidants, polyamines and nitrates contents were analyzed across different treatments. The plant growth was affected by the light quality - the presence of green light in the spectrum resulted in smaller plants and leaves, and correspondingly less biomass. RB spectral mode enhanced the total antioxidant and guaiacol peroxidase activity, pigments, flavonoids, polyphenols, ascorbate and polyamines contents. This effect under RB was combined with better leaf development compared to RGB and less nitrate in the leaves among all treatments. The RB light generated modifications in polyamines, which are interrelated with the nitrate content, further induce important metabolite and antioxidant changes. Both RB and RGB enhanced photosynthesis. The afterglow thermoluminescence band varied according to leaves development, being higher in RB and WL as a consequence of their faster growth. The RB light spectrum was found to be the most efficient for promoting the growth, biochemical composition, and overall quality of Eruca sativa compared to RGB and WL. These findings suggest that RB LEDs can be an effective tool for improving crop production in controlled environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Polyamines (PAs) along with their conjugated forms, are important mediators of plant defense mechanisms against both biotic and abiotic stresses. Flavin-containing polyamine oxidases (PAOs) regulate PA levels through terminal oxidation. To date, the role of PAOs in plant-herbivore interaction remains poorly understood. We discovered that infestation by the brown planthopper (BPH) disrupts PA homeostasis within the leaf sheaths of rice plants, which co-occurs with the upregulation of OsPAO6, a tissue-specific inducible, apoplast-localized enzyme that regulates the terminal catabolism of spermidine (Spd) and spermine. Functional analysis using CRISPR-Cas9 genome-edited plants revealed that pao6 mutants accumulated significantly higher levels of Spd and phenylpropanoid-conjugated Spd in response to BPH infestation compared to wild-type controls. In addition, BPH feeding on pao6 mutants led to increased honeydew excretion and plant damage by female adults, consistent with in vitro experiments in which Spd enhanced BPH feeding. Furthermore, OsPAO6 transcription is regulated by jasmonate (JA) signaling, and it is dependent on MYC2, which directly binds to the G-box-like motif in the OsPAO6 promoter. Our findings reveal an important role of OsPAO6 in regulating polyamine catabolism in JA-induced responses triggered by herbivore attacks in rice., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Metabolic dysregulation in the ischemic region has been increasingly recognized as a contributing factor to ischemic stroke pathogenesis. Taohong Siwu decoction (THSWD), a traditional Chinese medicine preparation used to enhance blood circulation, is frequently employed in treating ischemic stroke. However, the metabolic regulatory mechanism underlying the therapeutic effects of THSWD in ischemic stroke remains largely unexplored. In this study, we employed desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to investigate the metabolic changes in the brain tissue of ischemic stroke rat model. Our investigation revealed that 30 metabolites exhibited significant dysregulation in the ischemic brain regions, specifically the cortex and striatum, following ischemic injury. Following the treatment of THSWD, almost all the dysregulated metabolites got different degrees of callback. Further pathway analysis indicated that THSWD might exert its therapeutic effects by restoring energy metabolism, improving neurotransmitter metabolism, recovering polyamine metabolism, and so on. DESI-MSI offers a favorable methodology for investigating the alterations in the spatial distribution and level within the ischemic brain region following treatment with THSWD in ischemic stroke. These findings provide a novel perspective on the underlying mechanisms of the efficacy of THSWD in ischemic stroke treatment., Competing Interests: Declarations. Ethics approval: The use of laboratory animals and all study protocols were approved by the Animal Protection Committee and Use Committee of Anhui University of Chinese Medicine. Source of biological material: Male Sprague–Dawley rats (250 − 290 g) were provided by Liaoning Changsheng Biotechnology Co., Ltd. Statement on animal welfare: The management and use of animals during the experiment comply with the relevant regulations of “Guide for the Care and Use of Laboratory Animals issued by the National Research Council of the United States (2010),” “Regulations for the administration of affairs concerning laboratory animals (2017)” issued by the Science and Technology Commission of China, and the relevant regulations provided by the Animal Protection Committee and Use Committee of Anhui University of Chinese Medicine. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Accumulating evidence in recent years has demonstrated the important role of gut microbiota in maintaining cardiovascular function. However, their functions in abdominal aortic aneurysm (AAA) are largely unexplored. In this study, we established a porcine pancreatic elastase-infused experimental AAA mouse model and explored gut microbiota modulation using 16S rDNA sequencing. Here, we found that a significant alteration to gut microbiota composition and function occurred in AAA. The functional change in the gut microbiome revealed dysregulated biosynthesis metabolism and transport of spermidine in AAA. Furthermore, exogenous spermidine was administrated via drinking water and attenuated the progression of experimental AAA disease, which supports our recent study that spermidine alleviates systemic inflammation and AAA. These effects were associated with remitted gut microbiota dysbiosis and metabolism in AAA progression as demonstrated by 16S rDNA gene analysis. In addition, several bacterial florae, such as Bacteroides, Parabacteroides and Prevotella, were identified to be associated with the progression of AAA. Our results uncovered altered gut microbial profiles in AAA and highlighted the potential therapeutic use of spermidine in the treatment of gut microbiota dysbiosis and AAA. [ABSTRACT FROM AUTHOR]

Maize is a cold-sensitive crop, and it exhibits severe retardation of growth and development when exposed to cold snaps during and right after seedling emergence. Although different agronomic, physiological, and molecular approaches have been tried to overcome the problems related to cold stress in recent years, the mechanisms causing cold resistance in maize are still unclear. Screening and breeding of varieties for cold resistance may be a sustainable option to boost maize production under low-temperature environments. Herein, seedlings of 39 different maize genotypes were treated under both 10 °C low temperature and 22 °C normal temperature conditions for 7 days, to assess the changes in seven growth parameters, two membrane characteristics, two reactive oxygen species (ROS) levels, and four antioxidant enzymes activities. The changes in ten photosynthetic performances, one osmotic substance accumulation, and three polyamines (PAs) metabolisms were also measured. Results indicated that significant differences among genotypes, temperature treatments, and their interactions were found in 29 studied traits, and cold–stressed seedlings were capable to enhance their cold resistance by maintaining high levels of membrane stability index (66.07%); antioxidant enzymes activities including the activity of superoxide dismutase (2.44 Unit g−1 protein), peroxidase (1.65 Unit g−1 protein), catalase (0.65 μM min−1 g−1 protein), and ascorbate peroxidase (5.45 μM min−1 g−1 protein); chlorophyll (Chl) content, i.e., Chl a (0.36 mg g−1 FW) and Chl b (0.40 mg g−1 FW); photosynthetic capacity such as net photosynthetic rate (5.52 μM m−2 s−1) and ribulose 1,5–biphosphate carboxylase activity (6.57 M m−2 s−1); PAs concentration, mainly putrescine (274.89 nM g−1 FW), spermidine (52.69 nM g−1 FW), and spermine (45.81 nM g−1 FW), particularly under extended cold stress. Importantly, 16 traits can be good indicators for screening of cold–resistant genotypes of maize. Gene expression analysis showed that GRMZM2G059991, GRMZM2G089982, GRMZM2G088212, GRMZM2G396553, GRMZM2G120578, and GRMZM2G396856 involved in antioxidant enzymes activity and PAs metabolism, and these genes may be used for genetic modification to improve maize cold resistance. Moreover, seven strong cold–resistant genotypes were identified, and they can be used as parents in maize breeding programs to develop new varieties. [ABSTRACT FROM AUTHOR]

Kainate receptors (KARs) are a subtype of ionotropic glutamate receptor (iGluR) channels, a superfamily of ligand-gated ion channels which mediate the majority of excitatory neurotransmission in the central nervous system. KARs modulate neuronal circuits and plasticity during development and are implicated in neurological disorders, including epilepsy, depression, schizophrenia, anxiety, and autism. Calcium-permeable KARs undergo ion channel block, but the therapeutic potential of channel blockers remains underdeveloped, mainly due to limited structural knowledge. Here, we present closed-state structures of GluK2 KAR homotetramers in complex with ion channel blockers NpTx-8, PhTx-74, Kukoamine A, and spermine. We find that blockers reside inside the GluK2 ion channel pore, intracellular to the closed M3 helix bundle-crossing gate, with their hydrophobic heads filling the central cavity and positively charged polyamine tails spanning the selectivity filter. Molecular dynamics (MD) simulations of our structures illuminate interactions responsible for different affinity and binding poses of the blockers. Our structures elucidate the trapping mechanism of KAR channel block and provide a template for designing new blockers that can selectively target calcium-permeable KARs in neuropathologies., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Polyamines (PAs), such as putrescine, spermine, and spermidine, are bioactive molecules that play a vital role in plant responses to stresses. Although they are frequently applied to achieve higher levels of stress tolerance in plants, their function in seed biology is still not fully understood. PAs have been described in only a limited number of studies as seed priming agents, but most of the data report only the physiological and biochemical PA effects, and only a few reports concern the molecular mechanisms. In this review, we summarized PA seed priming effects on germination, seedling establishment, and young plant response to abiotic stresses, and tried to draw a general scheme of PA action during early developmental plant stages.

Fused in sarcoma (FUS) is involved in the formation of nuclear biomolecular condensates associated with poly(ADP-ribose) [PAR] synthesis catalyzed by a DNA damage sensor such as PARP1. Here, we studied FUS microphase separation induced by poly(ADP-ribosyl)ated PARP1 WT [PAR-PARP1 WT ] or its catalytic variants PARP1 Y986S and PARP1 Y986H , respectively, synthesizing (short PAR)-PARP1 Y986S or (short hyperbranched PAR)-PARP1 Y986H using dynamic light scattering, fluorescence microscopy, turbidity assays, and atomic force microscopy. We observed that biologically relevant cations such as Mg 2+ , Ca 2+ , or Mn 2+ or polyamines (spermine 4+ or spermidine 3+ ) were essential for the assembly of FUS with PAR-PARP1 WT and FUS with PAR-PARP1 Y986S in vitro. We estimated the range of the FUS-to-PAR-PARP1 molar ratio and the cation concentration that are favorable for the stability of the protein's microphase-separated state. We also found that FUS microphase separation induced by PAR-PARP1 Y986H (i.e., a PARP1 variant attaching short hyperbranched PAR to itself) can occur in the absence of cations. The dependence of PAR-PARP1-induced FUS microphase separation on cations and on the branching of the PAR structure points to a potential role of the latter in the regulation of the formation of FUS-related biological condensates and requires further investigation.

Polyamines are critical cellular components that regulate a variety of processes, including translation, cell cycling, and nucleic acid metabolism. The polyamines, putrescine, spermidine, and spermine, are found abundantly within cells and are positively-charged at physiological pH. Polyamine metabolism is connected to distinct other metabolic pathways, including nucleotide and amino acid metabolism. However, the breadth of the effect of polyamines on cellular metabolism remains to be fully understood. We recently demonstrated a role for polyamines in cholesterol metabolism, and following these studies, we measured the impact of polyamines on global lipid metabolism. We find that lipid droplets increase in number and size with polyamine depletion. We further demonstrate that lipid anabolism is markedly decreased, and lipid accumulation is due to reduced mitochondrial fatty acid oxidation. In fact, mitochondrial structure and function are largely ablated with polyamine depletion. To compensate, cells depleted of polyamines switch from aerobic respiration to glycolysis in a polyamine depletion-mediated Warburg-like effect. Finally, we show that inhibitors of lipid metabolism are broadly antiviral, suggesting that polyamines and lipids are promising antiviral targets. Together, these data demonstrate a novel role for polyamines in mitochondrial function, lipid metabolism, and cellular energetics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cruz-Pulido et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Polyamines are bioactive amines found in almost all living organisms and are essential for normal cellular functions [...].

Polyamines are polycationic molecules that are crucial in a wide array of cellular functions. Their biosynthesis is mediated by aminopropyl transferases (APTs), which are promising targets for antimicrobial, antineoplastic, and antineurodegenerative therapies. A major limitation in studying APT enzymes, however, is the lack of high-throughput assays to measure their activity. We have developed the first fluorescence-based assay, diacetyl benzene (DAB)-APT, for the measurement of APT activity using 1,2-DAB, which forms fluorescent conjugates with putrescine, spermidine, and spermine, with fluorescence intensity increasing with the carbon chain length. The assay has been validated using APT enzymes from Saccharomyces cerevisiae and Plasmodium falciparum, and the data further validated by mass spectrometry and TLC. Using mass spectrometry analysis, the structures of the fluorescent putrescine, spermidine, and spermine 1,2-DAB adducts were determined to be substituted 1,3-dimethyl isoindoles. The DAB-APT assay is optimized for high-throughput screening, facilitating the evaluation of large chemical libraries. Given the critical roles of APTs in infectious diseases, oncology, and neurobiology, the DAB-APT assay offers a powerful tool with broad applicability, poised to drive advancements in research and drug discovery., Competing Interests: Conflict of interest C. B. M. is listed on a provisional patent application on the use of DAB-APT assay and its use to discover inhibitors of APT enzymes. The other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Grapholita molesta is an important and harmful fruit pest worldwide, with widespread feeding hosts. Trypsin, an indispensable hydrolytic digestive protease in the insect gut, is crucial in digestion, growth and development. We analyzed the characteristics of the trypsin-encoding genes, screened for the optimal dose of RNAi mediated by nanocarriers, and investigated various indices of larval growth and development of G. molesta., Results: Gut content (GC) and RNase A degraded double-stranded RNA (dsRNA), with a faster degradation rate at higher concentrations. Star polycation (SPc) nanomaterials protected dsGFP from degradation by anion-cation binding and did not migrate through agarose gel. The key conserved motifs of the trypsin-encoding genes were similar, exhibiting high homology with those in other lepidopteran insects. An interference efficiency of ≈70% was achieved with SPc nanomaterial-mediated RNA interference with 0.05 μg dsRNA. The efficiency of continuous interference was stable. Trypsin activity, body weight of 8-day-old larvae, pupal weight and emergence rate were significantly reduced, and the larval stage was significantly prolonged., Conclusion: The investigated trypsin gene is a key target gene in the growth and development of G. molesta. We investigated the efficiency and convenience of feeding SPc nanomaterials in a functional study of insects. Our results provide valuable data for the development of efficient trypsin-targeting pesticides. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The aggregation of α-synuclein (α-syn) into amyloid fibrils, a key process in the development of Parkinson's disease (PD) and other synucleinopathies, is influenced by a range of factors such as charged biopolymers, chaperones, and metabolites. However, the specific impacts of different biopolymers on α-syn fibril structure are not well understood. In our work, we found that different polyanions and polycations, such as polyphosphate (polyP), polyuridine (polyU), and polyamines (including putrescine, spermidine, and spermine), markedly altered the fibrillation kinetics of α-syn in vitro. Furthermore, the seeding assay revealed distinct cross-seeding capacities across different biopolymer-induced α-syn fibrils, suggesting the formation of structurally distinct strains under different conditions. Utilizing cryo-electron microscopy (cryo-EM), we further examined the detailed structural configuration of α-syn fibrils formed in the presence of these biopolymers. Notably, we found that while polyamines do not change the atomic structure of α-syn fibrils, polyU and polyP induce the formation of distinct amyloid fibrils, exhibiting a range of structural polymorphs. Our work offers valuable insights into how various charged biopolymers affect the aggregation process and the resultant structures of α-syn fibrils, thereby enhancing our understanding of the structural variations in α-syn fibrils across different pathological conditions., Competing Interests: Conflict of interests The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The hypothalamic-pituitary-gonadal (HPG) axis is pivotal in regulating reproductive functions, with gonadotropin-releasing hormone (GnRH) acting as a central regulator. Recently, polyamines have been shown to regulate the HPG axis, including GnRH expression and ovarian biology in old and adult rodents. The present study firstly highlights the age-specific variation in the polyamine and their corresponding biosynthetic enzymes in the ovary during aging, and further, the study focuses on the effect of polyamines, putrescine, and agmatine, in young female mice., Method and Result: Immunofluorescence analysis revealed age-related differences in the expression of ornithine decarboxylase 1 (ODC1), spermine (SPM), and spermidine (SPD) in the ovaries, with adult mice exhibiting significantly higher expression levels compared to young and old mice. Likewise, qPCR analysis showed the mRNA levels of Odc1, Spermidine synthase (Srm), and Spermine synthase (Sms) show a significant increase in adult ovaries, which is then followed by a significant decline in old age. Histological examination demonstrated morphological alterations in the ovaries with age, including decreased follicle numbers and increased stromal cells in old mice. Furthermore, treatment with putrescine, a polyamine, in young mice resulted in larger ovaries and increased follicle numbers compared to controls. Additionally, serum levels of gonadotropin-releasing hormone (GnRH) and progesterone (P4) were measured, showing elevated levels in polyamine-treated mice. GnRH mRNA expression also increased significantly. Gene expression analysis revealed upregulation of genes associated with folliculogenesis such as Fshr, Bmp15, Gdf9, Amh, Star, Hsdb3, and Plaur in the ovaries and onset of puberty such as Tac2, and Kiss1, and a decrease in Mkrn3 in the hypothalamus of polyamine-treated mice., Conclusion: This study investigates the effect of polyamines in young immature female mice, shedding light on their role in upregulating GnRH, and enhancing folliculogenesis. Overall, these findings suggest that polyamines play a crucial role in ovarian aging and HPG axis regulation, offering potential therapeutics to reinstate fertility in reproductively challenged individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The overexpression of polyamines in tumor cells contributes to the establishment of immunosuppressive microenvironment and facilitates tumor growth. Here, it have ingeniously designed multifunctional copper-piceatannol/HA nanopills (Cu-Pic/HA NPs) that effectively cause total intracellular polyamines depletion by inhibiting polyamines synthesis, depleting intracellular polyamines, and impairing polyamines uptake, resulting in enhanced pyroptosis and cuproptosis, thus activating a powerful immune response to achieve anti-tumor therapy. Mitochondrial dysfunction resulting from overall intracellular polyamines depletion not only leads to the surge of copper ions in mitochondria, thereby causing the aggregation of toxic proteins to induce cuproptosis, but also triggers the accumulation of reactive oxygen species (ROS) within mitochondria, which further upregulates the expression of zDHHC5 and zDHHC9 to promote the palmitoylation of gasdermin D (GSDMD) and GSDMD-N, ultimately inducing enhanced pyroptosis. Then the occurrence of enhanced pyroptosis and cuproptosis is conductive to remodel the immunosuppressive tumor microenvironment, thus activating anti-tumor immune responses and ultimately effectively inhibiting tumor growth and metastasis. This therapeutic strategy of enhanced pyroptosis and cuproptosis through comprehensive polyamines depletion provides a novel template for cancer immunotherapy., (© 2024 Wiley‐VCH GmbH.)

Putrescine (Put) is a promising small molecule-based biostimulant to enhance plant growth and resilience, though its mode of action remains unclear. This study investigated the Put priming effect on Arabidopsis mutant lines (Atadc1, Atadc2, Atnata1, and Atnata2) under control conditions and salinity to understand its role in regulating plant growth. The Atadc2 mutant, characterized by reduced endogenous Put levels, showed insensitivity to Put priming without growth enhancement, which was linked to significant imbalances in nitrogen metabolism, including a high Gln/Glu ratio. Contrarily, the Atnata2 mutant exhibited significant growth improvement and upregulated AtADC2 expression, particularly under Put priming, highlighting these genes' involvement in regulating plant development. Put priming enhanced plant growth by inducing the accumulation of specific polyamines (free, acetylated, conjugated, or bound form) and improving light-harvesting efficiency, particularly in the Atnata2 line. Our findings suggest that AtNATA2 may negatively regulate Put synthesis and accumulation via AtADC2 in the chloroplast, impacting light harvesting in photosystem II (PSII). Furthermore, the Atadc2 mutant line exhibited upregulated AtADC1 but reduced AcPut levels, pointing to a cross-regulation among these genes. The regulation by AtNATA2 on AtADC2 and AtADC2 on AtADC1 could be crucial for plant growth and overall stress tolerance by interacting with polyamine catabolism, which shapes the plant metabolic profile under different growth conditions. Understanding the regulatory mechanisms involving crosstalk between AtADC and AtNATA genes in polyamine metabolism and the connection with certain SMBBs like Put can lead to more effective agricultural practices, improving plant growth, nitrogen uptake, and resilience under challenging conditions., (© 2024 The Author(s). Physiologia Plantarum published by John Wiley & Sons Ltd on behalf of Scandinavian Plant Physiology Society.)

Polyamines (PAs) are pleiotropic bioorganic molecules. Cellular PA contents are determined by a balance between PA synthesis and degradation. PAs have been extensively demonstrated to play vital roles in the modulation of plant developmental processes and adaptation to various environmental stresses. In this review, the latest advances on the diverse roles of PAs in a range of developmental processes, such as morphogenesis, organogenesis, growth and development, and fruit ripening, are summarized and discussed. Besides, the crosstalk between PAs and phytohormones or other signalling molecules, including H 2 O 2 and NO, involved in these processes is dwelled on. In addition, the attempts made to improve the yield and quality of grain and vegetable crops through altering the PA catabolism are enumerated. Finally, several other vital questions that remain unanswered are proposed and discussed. These include the mechanisms underlying the cooperative regulation of developmental processes by PAs and their interplaying partners like phytohormones, H 2 O 2 and NO; PA transport for maintaining homeostasis; and utilization of PA anabolism/catabolism for generating high-yield and good-quality crops. This review aims to gain new insights into the pleiotropic role of PAs in the modulation of plant growth and development, which provides an alternative approach for manipulating and engineering valuable crop varieties that can be used in the future., (© 2024 The Author(s). Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Antizyme (AZ) is a regulatory protein that plays a crucial role in modulating the activity of ornithine decarboxylase (ODC), which is the initial and rate-limiting enzyme in the complex pathway of polyamine biosynthesis. AZ facilitates the swift degradation of ODC, thereby modulating the levels of cellular polyamines. This study unveils a new ubiquitin-independent mechanism for AZ degradation, emphasizing the essential role of N-terminal degrons. Contrary to traditional ubiquitin-dependent degradation, our findings reveal that AZ degradation is significantly influenced by its N-terminal region. By conducting a series of experiments, including in vitro degradation assays, cycloheximide chase experiments, differential scanning calorimetry, and measurement of cellular concentrations of polyamines, we demonstrate that N-terminal truncation significantly enhances AZ's stability and facilitates the reduction of polyamine levels by accelerating ODC degradation. The removal of the N-terminal portion of AZ results in a reduced degradation rate and enhanced thermal stability of the protein, leading to a more efficient inhibition of polyamine synthesis. These findings are corroborated by the analysis of AZ isoforms, AZ1, AZ2, and AZ3, which display differential degradation patterns based on the specific N-terminal segments. This substantiates a degradation mechanism driven by an intrinsically disordered N-terminal region acting as a degron, independent of lysine ubiquitination. These results underscore the significant regulatory function of the N-terminal domain in the activity of AZ and the maintenance of polyamine homeostasis., (© 2024 The Protein Society.)

Rhizobia are common symbiotic microorganisms in the root system of leguminous plants that can usually provide nitrogen to the host through nitrogen fixation. Studies have shown that rhizobium-preinoculated soybean plants usually exhibit improved salt tolerance, but the underlying mechanism is not fully understood. In this paper, transcriptome sequencing (RNA-seq) revealed that preinoculation with rhizobia affected polyamine (PA) metabolism in soybean roots. The assay of PA contents showed that preinoculation with rhizobia significantly increased the putrescine (Put) content in roots and leaves during short-term salt treatment (0-5 d). Long-term salt treatment (5-7 d) resulted in a high Put content and significantly increased Spm and Spd contents, resulting in a rapid increase in the Put/(Spd + Spm) ratio (0-5 d) and subsequent decrease. Moreover, rhizobium preinoculation of soybean plants resulted in increased contents of conjugated and bound PAs under salt stress. Further transcriptome sequencing, PA contents, PA synthase expression and activity analysis revealed that GmADC may be a key gene related to salt tolerance in rhizobium-preinoculated soybean plants, and the GmADC-overexpressing soybean hairy-root composite plants exhibited less ROS damage, lower Cl - /NO 3 - ratios and Na + /K + ratios, and stabilized ion homeostasis. Taken together, preinoculation with rhizobia increased the expression level and enzyme activity of arginine decarboxylase (ADC) in soybean roots, increased the content of Put in roots and leaves, and increased the content of conjugated and bound PAs in soybean plants, thereby alleviating the oxidative and ionic injuries of soybean plants and enhancing the salt tolerance., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

The gut microbiota plays a critical role in numerous biochemical processes essential for human health, such as metabolic regulation and immune system modulation. An increasing number of research suggests a strong association between the gut microbiota and carcinogenesis. The diverse metabolites produced by gut microbiota can modulate cellular gene expression, cell cycle dynamics, apoptosis, and immune system functions, thereby exerting a profound influence on cancer development and progression. A healthy gut microbiota promotes substance metabolism, stimulates immune responses, and thereby maintains the long-term homeostasis of the intestinal microenvironment. When the gut microbiota becomes imbalanced and disrupts the homeostasis of the intestinal microenvironment, the risk of various diseases increases. This review aims to elucidate the impact of gut microbial metabolites on cancer initiation and progression, focusing on short-chain fatty acids (SCFAs), polyamines (PAs), hydrogen sulfide (H 2 S), secondary bile acids (SBAs), and microbial tryptophan catabolites (MTCs). By detailing the roles and molecular mechanisms of these metabolites in cancer pathogenesis and therapy, this article sheds light on dual effects on the host at different concentrations of metabolites and offers new insights into cancer research., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Intracellular metabolism is a crucial regulator of macrophage function. Recent evidence revealed that the polyamine pathway and subsequent hypusination of eukaryotic initiation factor 5A (eIF5A) are master regulators of immune cell functions. In brown adipose tissue (BAT), macrophages show an impressive degree of heterogenicity, with specific subsets supporting adaptive thermogenesis during cold exposure. In this review, we discuss the impact of polyamine metabolism on macrophage diversity and function, with a particular focus on their role in adipose tissue homeostasis. Thus, we highlight the exploration of how polyamine metabolism in macrophages contributes to BAT homeostasis as an attractive and exciting new field of research., Competing Interests: Declaration of interests None declared by authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Breast cancer remains the leading malignant neoplasm among women globally, posing significant challenges in terms of treatment and prognostic evaluation. The metabolic pathway of polyamines is crucial in breast cancer progression, with a strong association to the increased capabilities of tumor cells for proliferation, invasion, and metastasis., Methods: We used a multi-omics approach combining bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) to study polyamine metabolism. Data from The Cancer Genome Atlas, Gene Expression Omnibus, and Genotype-Tissue Expression identified 286 differentially expressed genes linked to polyamine pathways in breast cancer. These genes were analyzed using univariate COX and machine learning algorithms to develop a prognostic scoring algorithm. Single-cell RNA sequencing validated the model by examining gene expression heterogeneity at the cellular level., Results: Our single-cell analyses revealed distinct subpopulations with different expressions of genes related to polyamine metabolism, highlighting the heterogeneity of the tumor microenvironment. The SuperPC model (a constructed risk score) demonstrated high accuracy when predicting patient outcomes. The immune profiling and functional enrichment analyses revealed that the genes identified play a crucial role in cell cycle control and immune modulation. Single-cell validation confirmed that polyamine metabolism genes were present in specific cell clusters. This highlights their potential as therapeutic targets., Conclusions: This study integrates single cell omics with machine-learning to develop a robust scoring model for breast cancer based on polyamine metabolic pathways. Our findings offer new insights into tumor heterogeneity, and a novel framework to personalize prognosis. Single-cell technologies are being used in this context to enhance our understanding of the complex molecular terrain of breast cancer and support more effective clinical management., (© 2024. The Author(s).)

Polyamines (PAs), which are aliphatic polycationic compounds with a low molecular weight, are found in all living organisms and play essential roles in plant-pathogen interactions. Putrescine, spermidine, and spermine, the most common PAs in nature, respond to and function differently in plants and pathogens during their interactions. While plants use certain PAs to enhance their immunity, pathogens exploit PAs to facilitate successful invasion. In this review, we compile recent studies on the roles of PAs in plant-pathogen interactions, providing a comprehensive overview of their roles in both plant defense and pathogen pathogenicity. A thorough understanding of the functions of PAs and conjugated PAs highlights their potential applications in fungicide development. The creation of new fungicides and compounds derived from PAs demonstrates their promising potential for further research and innovation in this field.

Polyamines are involved in various functions related to the cellular-level responses. To assess effects of polyamines on marine organisms, rearing experiments and comprehensive gene expression analyses were conducted on Acropora digitifera and Acropora sp.1, representative reef-building corals along the west-central coast of Okinawa, Japan, to evaluate effects of putrescine. Concentrations of putrescine ≥ 1 mM dissolved tissues of juvenile polyps and increased mortality of planula larvae. RNA-Seq analysis of juvenile polyps exposed to putrescine at the stage before effects became visible revealed dynamic fluctuations in gene expression in the putrescine-treated samples, with increased expression of stress-responsive genes (e.g. NAD-dependent protein deacylase sirtuin-6) and the polyamine transporter Slc18b1-like protein. These results also suggest that putrescine affects expression of genes related to ribosomes and translation. This study provides important insights into roles of polyamines and future directions regarding physiological responses of corals., (© 2024. The Author(s).)

Gut microbiota plays a vital role in host metabolism; however, the influence of gut microbes on polyamine metabolism is unknown. Here, we found germ-free models possess elevated polyamine levels in the colon. Mechanistically, intestinal Lactobacillus murinus -derived small RNAs in extracellular vesicles down-regulate host polyamine metabolism by targeting the expression of enzymes in polyamine metabolism. In addition, Lactobacillus murinus delays recovery of dextran sodium sulfate-induced colitis by reducing polyamine levels in mice. Notably, a decline in the abundance of small RNAs was observed in the colon of mice with colorectal cancer (CRC) and human CRC specimens, accompanied by elevated polyamine levels. Collectively, our study identifies a specific underlying mechanism used by intestinal microbiota to modulate host polyamine metabolism, which provides potential intervention for the treatment of polyamine-associated diseases., Competing Interests: Competing interests statement:The authors declare no competing interest.

GABA (gamma-aminobutyric acid) is an amino acid whose numerous regulatory functions have been identified in animal organisms. More and more research indicate that in plants, this molecule is also involved in controlling basic growth and development processes. As recent studies have shown, GABA plays an essential role in triggering plant resistance to unfavorable environmental factors, which is particularly important in the era of changing climate. The main sources of GABA in plant cells are glutamic acid, converted in the GABA shunt pathway, and polyamines subjected to oxidative degradation. The action of GABA is often related to the activity of other messengers, including phytohormones, polyamines, NO, H 2 O 2 , or melatonin. GABA can function as an upstream or downstream element in the signaling pathways of other regulators, acting synergistically or antagonistically with them to control cellular processes. Understanding the role of GABA and its interactions with other signaling molecules may be important for developing crop varieties with characteristics that enable adaptation to a changing environment.

2-Aminoethanethiol dioxygenase (ADO) is a thiol dioxygenase that sulfinylates cysteamine and amino-terminal cysteines in polypeptides. The pathophysiological roles of ADO remain largely unknown. Here, we demonstrate that ADO expression represents a vulnerability in cancer cells, as ADO depletion led to loss of proliferative capacity and survival in cancer cells and reduced xenograft growth. In contrast, generation of the ADO knockout mouse revealed high tolerance for ADO depletion in adult tissues. To understand the mechanism underlying ADO's essentiality in cancer cells, we characterized the cell proteome and metabolome following depletion of ADO. This revealed that ADO depletion leads to toxic levels of polyamines which can be driven by ADO's substrate cysteamine. Polyamine accumulation in turn stimulated expression of proline dehydrogenase (PRODH) which resulted in mitochondrial hyperactivity and ROS production, culminating in cell toxicity. This work identifies ADO as a unique vulnerability in cancer cells, due to its essential role in maintenance of redox homeostasis through restraining polyamine levels and proline catabolism.

The increasing prevalence and severity of abiotic stresses on plants due to climate change is among the crucial issues of decreased crop productivity worldwide. These stresses affect crop productivity and pose a challenge to food security. Polyamines (Pas) and hydrogen peroxide (H₂O₂) could play a vital role to minimize the impact of several abiotic stresses on the plants. Pas are small molecules that regulate various physiological and developmental processes in plants and confer stress tolerance and protection against dehydration and cellular damage. Pas also interact with plant growth regulators and participate in various signaling routes that can mediate stress response. H₂O₂ on the other hand, acts as a signaling agent and plays a pivotal part in controlling crop growth and productivity. It can trigger oxidative damage at high levels but acts as a stress transducer and regulator at low concentrations. H₂O₂ is involved in stress defense mechanisms and the activation of genes involved in conferring tolerance. Therefore, the main focus of this paper is to explore roles of Pas and H₂O₂ in plant responses to various abiotic stress, highlighting their involvement in stress retaliation and signaling routes. Emphasis has been placed on understanding how Pas and H₂O₂ function and interact with other signaling molecules. Also, interaction of Pas and H₂O₂ with calcium ions, abscisic acid and nitrogen has been discussed, along with activation of MAPK cascade. This additive understanding could contribute to adopt strategies to improve crop productivity and enhance plant resilience to environmental challenges., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Breast cancer patients may initially benefit from cytotoxic chemotherapy but experience treatment resistance and relapse. Chemoresistant breast cancer stem cells (BCSCs) play a pivotal role in cancer recurrence and metastasis, however, identification and eradication of BCSC population in patients are challenging. Here, an mRNA-based BCSC signature is developed using machine learning strategy to evaluate cancer stemness in primary breast cancer patient samples. Using the BCSC signature, a critical role of polyamine anabolism in the regulation of chemotherapy-induced BCSC enrichment, is elucidated. Mechanistically, two key polyamine anabolic enzymes, ODC1 and SRM, are directly activated by transcription factor HIF-1 in response to chemotherapy. Genetic inhibition of HIF-1-controlled polyamine anabolism blocks chemotherapy-induced BCSC enrichment in vitro and in xenograft mice. A novel specific HIF-1 inhibitor britannin is identified through a natural compound library screening, and demonstrate that coadministration of britannin efficiently inhibits chemotherapy-induced HIF-1 transcriptional activity, ODC1 and SRM expression, polyamine levels, and BCSC enrichment in vitro and in xenograft and autochthonous mouse models. The findings demonstrate the key role of polyamine anabolism in BCSC regulation and provide a new strategy for breast cancer treatment., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Aged hematopoietic stem cells (HSCs) show reduced reconstitution potential, limiting their use in transplantation settings in the clinic. We demonstrate here that exposure of aged HSCs ex vivo to a pH of 6.9 instead of the commonly used pH of 7.4 results in enhanced HSCs potential that is consistent with rejuvenation, including attenuation of the myeloid bias of aged HSC and restoration of a youthful frequency of epigenetic polarity. Rejuvenation of aged HSCs by pH 6.9 is, at least in part, due to alterations in the polyamine/methionine pathway within pH 6.9 HSCs, and consequently, attenuation of the production of spermidine also attenuated aging of HSCs. Exposure of aged HSCs to pH 6.9, or pharmacological targeting of the polyamine pathway, might thus extend the use of HSCs from aged donors for therapeutic applications., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Globally, metal/metalloid(s) soil contamination is a persistent issue that affects the atmosphere, soil, water and plant health in today's industrialised world. However, an overabundance of these transition ions promotes the excessive buildup of reactive oxygen species (ROS) and ion imbalance, which harms agricultural productivity. Plants employ several strategies to overcome their negative effects, including hyperaccumulation, tolerance, exclusion, and chelation with organic molecules. Polyamines (PAs) are the organic compounds that act as chelating agents and modulate various physiological, biochemical, and molecular processes under metal/metalloid(s) stress. Their catabolic products, including H 2 O 2 and gamma amino butyric acid (GABA), are also crucial signalling molecules in abiotic stress situations, particularly under metal/metalloid(s) stress. In this review, we explained how PAs regulate genes and enzymes, particularly under metal/metalloid(s) stress with a specific focus on arsenic (As), boron (B), cadmium (Cd), chromium (Cr), and zinc (Zn). The PAs regulate various plant stress responses by crosstalking with other plant hormones, upregulating phytochelatin, and metallothionein synthesis, modulating stomatal closure and antioxidant capacity. This review presents valuable insights into how PAs use a variety of tactics to reduce the harmful effects of metal/metalloid(s) through multifaceted strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)