A phosphate starvation response-centered network regulates mycorrhizal symbiosis.

To secure phosphorus (P) from soil, most land plants use a direct phosphate uptake pathway via root hairs and epidermis and an indirect phosphate uptake pathway via mycorrhizal symbiosis. The interaction between these two pathways is unclear. Here, we mapped a network between transcription factors and mycorrhizal symbiosis-related genes using Y1H. Intriguingly, this gene regulatory network is governed by the conserved P-sensing pathway, centered on phosphate starvation response (PHR) transcription factors. PHRs are required for mycorrhizal symbiosis and regulate symbiosis-related genes via the P1BS motif. SPX-domain proteins suppress OsPHR2-mediated induction of symbiosis-related genes and inhibit mycorrhizal infection. In contrast, plants overexpressing OsPHR2 show improved mycorrhizal infection and are partially resistant to P-mediated inhibition of symbiosis. Functional analyses of network nodes revealed co-regulation of hormonal signaling and mycorrhizal symbiosis. This network deciphers extensive regulation of mycorrhizal symbiosis by endogenous and exogenous signals and highlights co-option of the P-sensing pathway for mycorrhizal symbiosis.

Liquid-Liquid Phase Transition Drives Intra-chloroplast Cargo Sorting.

In eukaryotic cells, organelle biogenesis is pivotal for cellular function and cell survival. Chloroplasts are unique organelles with a complex internal membrane network. The mechanisms of the migration of imported nuclear-encoded chloroplast proteins across the crowded stroma to thylakoid membranes are less understood. Here, we identified two Arabidopsis ankyrin-repeat proteins, STT1 and STT2, that specifically mediate sorting of chloroplast twin arginine translocation (cpTat) pathway proteins to thylakoid membranes. STT1 and STT2 form a unique hetero-dimer through interaction of their C-terminal ankyrin domains. Binding of cpTat substrate by N-terminal intrinsically disordered regions of STT complex induces liquid-liquid phase separation. The multivalent nature of STT oligomer is critical for phase separation. STT-Hcf106 interactions reverse phase separation and facilitate cargo targeting and translocation across thylakoid membranes. Thus, the formation of phase-separated droplets emerges as a novel mechanism of intra-chloroplast cargo sorting. Our findings highlight a conserved mechanism of phase separation in regulating organelle biogenesis.

When translation elongation is impaired, the mRNA is uniformly destabilized by the RNA degradosome, while the concentration of mRNA is altered along the molecule.

mRNA sits at the crossroads of transcription, translation and mRNA degradation. Many questions remain about the coupling of these three processes in Escherichia coli and, in particular, how translation may have an effect on mRNA degradation and transcription. To characterize the interplay between mRNA degradation and translation while accounting for transcription, we altered the translation initiation or elongation and measured the effects on mRNA stability and concentration. Using a mapping method, we analysed mRNA concentration and stability at the local scale all along the transcript. We showed that a decrease in translation initiation efficiency destabilizes the mRNA and leads to a uniform decrease in mRNA concentration throughout the molecule. Prematurely terminating translation elongation by inserting a stop codon is associated with a drop in local mRNA concentration downstream of the stop codon, due to the uncoupling of transcription and translation. In contrast, this translation alteration uniformly destabilizes the coding and ribosome-free regions, in a process triggered by RNase E activity, and its ability to form the RNA degradome. These results demonstrate how ribosomes protect mRNA molecules and highlight how translation, mRNA degradation and transcription are deeply interconnected in the quality control process that avoids unproductive gene expression in cells.

Let-7 underlies metformin-induced inhibition of hepatic glucose production.

SignificanceA clear mechanistic understanding of metformin's antidiabetic effects is lacking. This is because suprapharmacological concentrations of metformin have been used in most studies. Using mouse models and human primary hepatocytes, we show that metformin, at clinically relevant doses, suppresses hepatic glucose production by activating a conserved regulatory pathway encompassing let-7, TET3, and a fetal isoform of hepatocyte nuclear factor 4 alpha (HNF4α). We demonstrate that metformin no longer has potent antidiabetic actions in a liver-specific let-7 loss-of-function mouse model and that hepatic delivery of let-7 ameliorates hyperglycemia and improves glucose homeostasis. Our results thus reveal an important role of the hepatic let-7/TET3/HNF4α axis in mediating the therapeutic effects of metformin and suggest that targeting this axis may be a potential therapeutic for diabetes.

Quantum Griffiths Singularity in Ordered Artificial Superconducting-Islands-Array on Graphene.

Quantum Griffiths phase (QGP) is a novel quantum phenomenon of quantum phase transition in two-dimensional (2D) superconductors, and the emergence of inhomogeneous superconducting rare regions immersed in a metallic matrix is theoretically related to the quantum Griffiths singularity (QGS). However, the theoretical proposal of superconducting rare regions still lacks intuitive experimental verification. Here, we construct an artificial ordered superconducting-islands-array on monolayer graphene with the aid of an anodic aluminum oxide (AAO) membrane. The QGS under both in-plane and out-of-plane magnetic fields is evidenced by the divergent dynamical critical exponent and is in compliance with the direct activated scaling behavior. The phase diagram clearly shows that the QGP is indeed bred in the rare superconducting regions within isolated superconducting islands with a vanished quantum coherence. Our results reveal the universal features of QGP in artificial heterostructured systems and provide a visualized platform for the theoretical proposal of QGS.

Coexistence of Ferromagnetism and Superconductivity at KTaO3 Heterointerfaces.

The coexistence of superconductivity and ferromagnetism is a long-standing issue in superconductivity due to the antagonistic nature of these two ordered states. Experimentally identifying and characterizing novel heterointerface superconductors that coexist with magnetism presents significant challenges. Here, we report the observation of two-dimensional long-range ferromagnetic order in a KTaO3 heterointerface superconductor, showing the coexistence of superconductivity and ferromagnetism. Remarkably, our direct current superconducting quantum interference device measurements reveal an in-plane magnetization hysteresis loop persisting above room temperature. Moreover, first-principles calculations and X-ray magnetic circular dichroism measurements provide decisive insights into the origin of the observed robust ferromagnetism, attributing it to oxygen vacancies that localize electrons in nearby Ta 5d states. Our findings suggest KTaO3 heterointerfaces as time-reversal symmetry breaking superconductors, injecting fresh momentum into the exploration of the intricate interplay between superconductivity and magnetism enhanced by the strong spin-orbit coupling inherent to the heavy Ta in 5d orbitals.

Selective Hydrofunctionalization of Alkenyl Fluorides Enabled by Nickel-Catalyzed Hydrogen Atoms and Group Transfer: Reaction Development and Mechanistic Study.

Due to the unique effect of fluorine atoms, the efficient construction of high-value alkyl fluorides has attracted significant interest in modern drug development. However, enantioselective catalytic strategies for the efficient assembly of highly functionalized chiral C(sp3)-F scaffolds from simple starting materials have been underutilized. Herein, we demonstrate a nickel-catalyzed radical transfer strategy for the efficient, modular, asymmetric hydrogenation and hydroalkylation of alkenyl fluorides with primary, secondary, and tertiary alkyl halides under mild conditions. The transformation provides facile access to various structurally complex secondary and tertiary α-fluoro amide products from readily available starting materials with excellent substrate compatibility and distinct selectivity. Furthermore, the utility of this method is demonstrated by late-stage modifications and product derivatizations. Detailed mechanistic studies and DFT calculations have been conducted, showing that the rate-determining step for asymmetric hydrogenation reaction is NiH-HAT toward alkenyl fluorides and the stereo-determining step is alcohol coordination to Ni-enolates followed by a barrierless protonation. The mechanism for the asymmetric hydroalkylation reaction is also delivered in this investigation.

A Wearable Electrochemical Biosensor Utilizing Functionalized Ti3C2Tx MXene for the Real-Time Monitoring of Uric Acid Metabolite.

Wearable, noninvasive sensors enable the continuous monitoring of metabolites in sweat and provide clinical information related to an individual's health and disease states. Uric acid (UA) is a key indicator highly associated with gout, hyperuricaemia, hypertension, kidney disease, and Lesch-Nyhan syndrome. However, the detection of UA levels typically relies on invasive blood tests. Therefore, developing a wearable device for noninvasive monitoring of UA concentrations in sweat could facilitate real-time personalized disease prevention. Here, we introduce 1,3,6,8-pyrene tetrasulfonic acid sodium salt (PyTS) as a bifunctional molecule functionalized with Ti3C2Tx via π-π conjugation to design nonenzymatic wearable sensors for sensitive and selective detection of UA concentration in human sweat. PyTS@Ti3C2Tx provides many oxidation-reduction active groups to enhance the electrocatalytic ability of the UA oxidation reaction. The PyTS@Ti3C2Tx-based electrochemical sensor demonstrates highly sensitive detection of UA in the concentration range of 5 µM-100 µM, exhibiting a lower detection limit of 0.48 µM compared to the uricase-based sensor (0.84 µM). In volunteers, the PyTS@Ti3C2Tx-based wearable sensor is integrated with flexible microfluidic sweat sampling and wireless electronics to enable real-time monitoring of UA levels during aerobic exercise. Simultaneously, it allows for comparison of blood UA levels via a commercial UA analyzer. Herein, this study provides a promising electrocatalyst strategy for nonenzymatic electrochemical UA sensor, enabling noninvasive real-time monitoring of UA levels in human sweat and personalized disease prevention.

Adolescent administration of ketamine impairs excitatory synapse formation onto parvalbumin-positive GABAergic interneurons in mouse prefrontal cortex.

Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, induces deficits in cognition and information processing following chronic abuse. Adolescent ketamine misuse represents a significant global public health issue; however, the neurodevelopmental mechanisms underlying this phenomenon remain largely elusive. This study investigated the long-term effects of sub-chronic ketamine (Ket) administration on the medial prefrontal cortex (mPFC) and associated behaviors. In this study, Ket administration during early adolescence displayed a reduced density of excitatory synapses on parvalbumin (PV) neurons persisting into adulthood. However, the synaptic development of excitatory pyramidal neurons was not affected by ketamine administration. Furthermore, the adult Ket group exhibited hyperexcitability and impaired socialization and working memory compared to the saline (Sal) administration group. These results strongly suggest that sub-chronic ketamine administration during adolescence results in functional deficits that persist into adulthood. Bioinformatic analysis indicated that the gene co-expression module1 (M1) decreased expression after ketamine exposure, which is crucial for synapse development in inhibitory neurons during adolescence. Collectively, these findings demonstrate that sub-chronic ketamine administration irreversibly impairs synaptic development, offering insights into potential new therapeutic strategies.

Boosting Reactive Oxygen Species Formation Over Pd and VOδ Co-Modified TiO2 for Methane Oxidation into Valuable Oxygenates.

Direct photocatalytic methane oxidation into value-added products provides a promising strategy for methane utilization. However, the inefficient generation of reactive oxygen species (ROS) partly limits the activation of CH4. Herein, it is reported that Pd and VOδ co-modified TiO2 enables direct and selective methane oxidation into liquid oxygenates in the presence of O2 and H2. Due to the extra ROS production from the in situ formed H2O2, a highly improved yield rate of 5014 µmol g-1 h-1 for liquid oxygenates with a selectivity of 89.3% is achieved over the optimized Pd0.5V0.2-TiO2 catalyst at ambient temperature, which is much better than those (2682 µmol g-1 h-1, 77.8%) without H2. Detailed investigations also demonstrate the synergistic effect between Pd and VOδ species for enhancing the charge carrier separation and transfer, as well as improving the catalytic activity for O2 reduction and H2O2 production.

OncoPubMiner: a platform for mining oncology publications.

Updated and expert-quality knowledge bases are fundamental to biomedical research. A knowledge base established with human participation and subject to multiple inspections is needed to support clinical decision making, especially in the growing field of precision oncology. The number of original publications in this field has risen dramatically with the advances in technology and the evolution of in-depth research. Consequently, the issue of how to gather and mine these articles accurately and efficiently now requires close consideration. In this study, we present OncoPubMiner (https://oncopubminer.chosenmedinfo.com), a free and powerful system that combines text mining, data structure customisation, publication search with online reading and project-centred and team-based data collection to form a one-stop 'keyword in-knowledge out' oncology publication mining platform. The platform was constructed by integrating all open-access abstracts from PubMed and full-text articles from PubMed Central, and it is updated daily. OncoPubMiner makes obtaining precision oncology knowledge from scientific articles straightforward and will assist researchers in efficiently developing structured knowledge base systems and bring us closer to achieving precision oncology goals.

Self-supervised semantic segmentation of retinal pigment epithelium cells in flatmount fluorescent microscopy images.

MOTIVATION: Morphological analyses with flatmount fluorescent images are essential to retinal pigment epithelial (RPE) aging studies and thus require accurate RPE cell segmentation. Although rapid technology advances in deep learning semantic segmentation have achieved great success in many biomedical research, the performance of these supervised learning methods for RPE cell segmentation is still limited by inadequate training data with high-quality annotations. RESULTS: To address this problem, we develop a Self-Supervised Semantic Segmentation (S4) method that utilizes a self-supervised learning strategy to train a semantic segmentation network with an encoder-decoder architecture. We employ a reconstruction and a pairwise representation loss to make the encoder extract structural information, while we create a morphology loss to produce the segmentation map. In addition, we develop a novel image augmentation algorithm (AugCut) to produce multiple views for self-supervised learning and enhance the network training performance. To validate the efficacy of our method, we applied our developed S4 method for RPE cell segmentation to a large set of flatmount fluorescent microscopy images, we compare our developed method for RPE cell segmentation with other state-of-the-art deep learning approaches. Compared with other state-of-the-art deep learning approaches, our method demonstrates better performance in both qualitative and quantitative evaluations, suggesting its promising potential to support large-scale cell morphological analyses in RPE aging investigations. AVAILABILITY AND IMPLEMENTATION: The codes and the documentation are available at: https://github.com/jkonglab/S4_RPE.

Blaming the unvaccinated during the COVID-19 pandemic: the roles of political ideology and risk perceptions in the USA.

Individuals unvaccinated against COVID-19 (C19) experienced prejudice and blame for the pandemic. Because people vastly overestimate C19 risks, we examined whether these negative judgements could be partially understood as a form of scapegoating (ie, blaming a group unfairly for an undesirable outcome) and whether political ideology (previously shown to shape risk perceptions in the USA) moderates scapegoating of the unvaccinated. We grounded our analyses in scapegoating literature and risk perception during C19. We obtained support for our speculations through two vignette-based studies conducted in the USA in early 2022. We varied the risk profiles (age, prior infection, comorbidities) and vaccination statuses of vignette characters (eg, vaccinated, vaccinated without recent boosters, unvaccinated, unvaccinated-recovered), while keeping all other information constant. We observed that people hold the unvaccinated (vs vaccinated) more responsible for negative pandemic outcomes and that political ideology moderated these effects: liberals (vs conservatives) were more likely to scapegoat the unvaccinated (vs vaccinated), even when presented with information challenging the culpability of the unvaccinated known at the time of data collection (eg, natural immunity, availability of vaccines, time since last vaccination). These findings support a scapegoating explanation for a specific group-based prejudice that emerged during the C19 pandemic. We encourage medical ethicists to examine the negative consequences of significant C19 risk overestimation among the public. The public needs accurate information about health issues. That may involve combating misinformation that overestimates and underestimates disease risk with similar vigilance to error.

Development of an ultra-high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of crassicauline A, fuziline, karacoline, and songorine in rat plasma and application in their pharmacokinetics.

In this paper, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for quantifying the levels of crassicauline A, fuziline, karacoline, and songorine in rat plasma. After processing the rat plasma, the proteins in the plasma were separated by extracting the analytes with acetonitrile-methanol (9:1, v/v). The chromatographic column used was the UPLC HSS T3 column, and the mobile phase (methanol-water with 0.1% formic acid) under a gradient elution profile was used to separate the four compounds, with elution times for each analyte being less than 5 min. Electrospray ionization in positive-ion mode and operating in multiple reaction monitoring mode was used for quantitative analysis. Crassicauline A, fuziline, karacoline, and songorine were administered to 48 rats (n = 6 per group) orally (5 mg/kg) and intravenously (0.5 mg/kg). The standard curves demonstrated excellent linearity in the range of 1-2500 ng/mL, wherein all r values were greater than 0.99. The UPLC-MS/MS method for the determination of crassicauline A, fuziline, karacoline, and songorine in rat plasma was successfully applied in determining their pharmacokinetics parameters, from which their oral bioavailabilities were calculated to be 18.7%, 4.3%, 6.0%, and 8.4%, respectively.

3-Methyl-4-nitrophenol Exposure Deteriorates Oocyte Maturation by Inducing Spindle Instability and Mitochondrial Dysfunction.

3-methyl-4-nitrophenol (PNMC), a well-known constituent of diesel exhaust particles and degradation products of insecticide fenitrothion, is a widely distributed environmental contaminant. PNMC is toxic to the female reproductive system; however, how it affects meiosis progression in oocytes is unknown. In this study, in vitro maturation of mouse oocytes was applied to investigate the deleterious effects of PNMC. We found that exposure to PNMC significantly compromised oocyte maturation. PNMC disturbed the spindle stability; specifically, it decreased the spindle density and increased the spindle length. The weakened spindle pole location of microtubule-severing enzyme Fignl1 may result in a defective spindle apparatus in PNMC-exposed oocytes. PNMC exposure induced significant mitochondrial dysfunction, including mitochondria distribution, ATP production, mitochondrial membrane potential, and ROS accumulation. The mRNA levels of the mitochondria-related genes were also significantly impaired. Finally, the above-mentioned alterations triggered early apoptosis in the oocytes. In conclusion, PNMC exposure affected oocyte maturation and quality through the regulation of spindle stability and mitochondrial function.

Removal of Sb(V) from complex wastewater of Sb(V) and aniline aerofloat using Fe3O4-CeO2 absorbent enhanced by H2O2: Efficiency and mechanism.

Effective elimination of heavy metals from complex wastewater is of great significance for industrial wastewater treatment. Herein, bimetallic adsorbent Fe3O4-CeO2 was prepared, and H2O2 was added to enhance Sb(V) adsorption by Fe3O4-CeO2 in complex wastewater of Sb(V) and aniline aerofloat (AAF) for the first time. Fe3O4-CeO2 showed good adsorption performance and could be rapidly separated by external magnetic field. After five adsorption/desorption cycles, Fe3O4-CeO2 still maintained good stability. The maximum adsorption capacities of Fe3O4-CeO2 in single Sb(V), AAF + Sb(V), and H2O2+AAF + Sb(V) systems were 77.33, 70.14, and 80.59 mg/g, respectively. Coexisting AAF inhibited Sb(V) adsorption. Conversely, additional H2O2 promoted Sb(V) removal in AAF + Sb(V) binary system, and made the adsorption capacity of Fe3O4-CeO2 increase by 14.90%. H2O2 could not only accelerate the reaction rate, but also reduce the optimal amount of adsorbent from 2.0 g/L to 1.2 g/L. Meanwhile, coexisting anions had little effect on Sb(V) removal by Fe3O4-CeO2+H2O2 process. The adsorption behaviors of Sb(V) in three systems were better depicted by pseudo-second-order kinetics, implying that the chemisorption was dominant. The complexation of AAF with Sb(V) hindered the adsorption of Sb(V) by Fe3O4-CeO2. The complex Sb(V) was oxidized and decomposed into free state by hydroxyl radicals produced in Fe3O4-CeO2+H2O2 process. Then the free Sb(V) was adsorbed by Fe3O4-CeO2 mostly through outer-sphere complexation. This work provides a new tactic for the treatment of heavy metal-organics complex wastewater.

Spinetoram-Induced Potential Neurotoxicity through Autophagy Mediated by Mitochondrial Damage.

Spinetoram is an important semi-synthetic insecticide extensively applied in agriculture. It is neurotoxic to insects, primarily by acting on acetylcholine receptors (nAChRs). However, few studies have examined the neurotoxicity of spinetoram in human beings. In this study, various concentrations (5, 10, 15, and 20 µM) of spinetoram were employed to expose SH-SY5Y cells in order to study the neurotoxic effects of spinetoram. The results showed that spinetoram exposure markedly inhibited cell viability and induced oxidative stress. It also induced mitochondrial membrane potential collapse (ΔΨm), and then caused a massive opening of the mitochondrial permeability transition pore (mPTP), a decrease in ATP synthesis, and Ca2+ overloading. Furthermore, spinetoram exposure induced cellular autophagy, as evidenced by the formation of autophagosomes, the conversion of LC3-I into LC3-II, down-regulation of p62, and up-regulation of beclin-1. In addition, we observed that p-mTOR expression decreased, while p-AMPK expression increased when exposed to spinetoram, indicating spinetoram triggered AMPK/mTOR-mediated autophagy. Complementarily, the effect of spinetoram on neurobehavior was studied using the zebrafish model. After being exposed to different concentrations (5, 10, and 20 µg/mL) of spinetoram, zebrafish showed neurobehavioral irregularities, such as reduced frequency of tail swings and spontaneous movements. Similarly, autophagy was also observed in zebrafish. In conclusion, spinetoram exposure produced potential neurotoxicity through autophagy mediated by mitochondrial damage. The experimental data and results of the neurotoxicity study of spinetoram provided above are intended to serve as reference for its safety assessment.

Delocalization Engineering of Heme-Mimetic Artificial Enzymes for Augmented Reactive Oxygen Catalysis.

Developing artificial enzymes based on organic molecules or polymers for reactive oxygen species (ROS)-related catalysis has broad applicability. Herein, inspired by porphyrin-based heme mimics, we report the synthesis of polyphthalocyanine-based conjugated polymers (Fe-PPc-AE) as a new porphyrin-evolving structure to serve as efficient and versatile artificial enzymes for augmented reactive oxygen catalysis. Owing to the structural advantages, such as enhanced π-conjugation networks and π-electron delocalization, promoted electron transfer, and unique Fe-N coordination centers, Fe-PPc-AE showed more efficient ROS-production activity in terms of Vmax and turnover numbers as compared with porphyrin-based conjugated polymers (Fe-PPor-AE), which also surpassed reported state-of-the-art artificial enzymes in their activity. More interestingly, by changing the reaction medium and substrates, Fe-PPc-AE also revealed significantly improved activity and environmental adaptivity in many other ROS-related biocatalytic processes, validating the potential of Fe-PPc-AE to replace conventional (poly)porphyrin-based heme mimics for ROS-related catalysis, biosensors, or biotherapeutics. It is suggested that this study will offer essential guidance for designing artificial enzymes based on organic molecules or polymers.

Translational repression of FZP mediated by CU-rich element/OsPTB interactions modulates panicle development in rice.

Panicle development is an important determinant of the grain number in rice. A thorough characterization of the molecular mechanism underlying panicle development will lead to improved breeding of high-yielding rice varieties. Frizzy Panicle (FZP), a critical gene for panicle development, is regulated by OsBZR1 and OsARFs at the transcriptional stage. However, the translational modulation of FZP has not been reported. We reveal that the CU-rich elements (CUREs) in the 3' UTR of the FZP mRNA are crucial for efficient FZP translation. The knockout of CUREs in the FZP 3' UTR or the over-expression of the FZP 3' UTR fragment containing CUREs resulted in an increase in FZP mRNA translation efficiency. Moreover, the number of secondary branches (NSB) and the grain number per panicle (GNP) decreased in the transformed rice plants. The CUREs in the 3' UTR of FZP mRNA were verified as the targets of the polypyrimidine tract-binding proteins OsPTB1 and OsPTB2 in rice. Both OsPTB1 and OsPTB2 were highly expressed in young panicles. The knockout of OsPTB1/2 resulted in an increase in the FZP translational efficiency and a decrease in the NSB and GNP. Furthermore, the over-expression of OsPTB1/2 decreased the translation of the reporter gene fused to FZP 3' UTR in vivo and in vitro. These results suggest that OsPTB1/2 can mediate FZP translational repression by interacting with CUREs in the 3' UTR of FZP mRNA, leading to changes in the NSB and GNP. Accordingly, in addition to transcriptional regulation, FZP expression is also fine-tuned at the translational stage during rice panicle development.

Dietary supplement use among adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort Study.

BACKGROUND: Adult survivors of childhood cancer have poor adherence to nutrition guidelines and inadequate intake of dietary vitamins D and E, potassium, fiber, magnesium, and calcium. The contribution of vitamin and mineral supplement use to total nutrient intake in this population is unclear. METHODS: We examined the prevalence and dose of nutrient intake among 2570 adult survivors of childhood cancer participating in the St. Jude Lifetime Cohort Study, and the association of dietary supplement use with treatment exposures, symptom burden, and quality of life. RESULTS: Nearly 40% of the adult survivors of cancer survivors reported regular use of dietary supplements. Although cancer survivors who used dietary supplements were less likely to have inadequate intake of several nutrients, they were also more likely to have excessive intake (total nutrient intake ≥ tolerable upper intake levels) of folate (15.4% vs. 1.3%), vitamin A (12.2% vs. 0.2%), iron (27.8% vs. 1.2%), zinc (18.6% vs. 1%), and calcium (5.1% vs. 0.9%) compared with survivors who did not use dietary supplements (all p < 0.05). Treatment exposures, symptom burden, and physical functioning were not associated with supplement use, whereas emotional well-being and vitality were positively associated with supplement use among childhood cancer survivors. CONCLUSIONS: Supplement use is associated with both inadequate and excessive intake of specific nutrients, but positively impacts aspects of quality of life among childhood cancer survivors.