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Cell surface proteins participate in many important biological processes, such as cell-to-cell interaction, signal transduction, cell adhesion, and protein transportation. In-depth study of the cell surface protein group is of great significance. Nevertheless, detection and analysis of the surfaceome remain a significant challenge due to their low abundance and hydrophobicity. Herein, we reported an ultrafast and chemoselective labeling method using our newly developed trifunctional probe, the OPA-S-S-alkyne, which labeled cell surface lysine residues, and then established a novel cell surfaceome profiling approach. According to our experimental results, the OPA-S-S-alkyne probe can react extremely fast with living cells, labeling cells in only 1 min, while traditional NHS (labeling cell surface lysine with N-hydroxysuccinimide ester probe) and CSC (labeling cell surface glycan with hydrazide biotin probe) methods normally take longer time of more than 30 min and 1 h, respectively. Taking advantage of this ultrafast property of the method, we highlight the utility of this method by exploring the temporal dynamic changes of surfaceome upon EGF stimulation in living Hela cells and reported "early" and "late" EGF-regulated cell surface proteins, which are difficult to be distinguished by the current cell surface profiling approaches.
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Protein modification by lipid-derived electrophiles (LDEs) is associated with various signaling pathways. Among these LDEs, 4-hydroxy-2-nonenal (HNE) is the most toxic, and protein modified with HNE has been linked to various diseases, including Alzheimer's and Parkinson's. However, due to their low abundance, in-depth profiling of HNE modifications still presents challenges. This study introduces a novel strategy utilizing reversible thiazolidine chemistry to selectively capture HNE-modified proteins and a palladium-mediated cleavage reaction to release them. Thousands of HNE-modified sites in different cell lines were identified. Combined with ABPP, we discovered a set of HNE-sensitive sites that offer a new tool for studying LDE modifications in proteomes.
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Aldehídos , Procesamiento Proteico-Postraduccional , Tiazolidinas , Aldehídos/metabolismo , Proteoma/metabolismo , Peroxidación de LípidoRESUMEN
Compensating for the intrinsic attosecond chirp (atto-chirp) of wideband high-order harmonics in the water window region is a significant challenge, in order to obtain isolated attosecond pulses (IAPs) with a width of tens of attoseconds (as). Here, we propose to realize the generation of IAP with duration as short as 20 as, central energy of 365 eV, and bandwidth exceeding 150 eV from chirp-free high harmonics generated by a four-color driving laser, without the necessity for atto-chirp compensation with natural materials. Unlike any other gating methods that an IAP arises from only one electron ionization event, we take advantage of the interference between harmonic radiation produced by multiple ionizing events. We further demonstrate that such chirp-free short IAP survives after taking account of macroscopic propagation effects. Given that the synthesized multicolor laser field can also effectively increase the harmonic flux, this work provides a practical way for experiments to generate the broad bandwidth chirp-free IAPs in the water window region.
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Evidence shows that tropomodulin 1 (TMOD1) is a powerful diagnostic marker in the progression of several cancer types. However, the regulatory mechanism of TMOD1 in tumor progression is still unclear. Here, we showed that TMOD1 was highly expressed in acute myeloid leukemia (AML) specimens, and TMOD1-silencing inhibited cell proliferation by inducing autophagy in AML THP-1 and MOLM-13 cells. Mechanistically, the C-terminal region of TMOD1 directly bound to KPNA2, and TMOD1-overexpression promoted KPNA2 ubiquitylation and reduced KPNA2 levels. In contrast, TMOD1-silencing increased KPNA2 levels and facilitated the nuclear transfer of KPNA2, then subsequently induced autophagy and inhibited cell proliferation by increasing the nucleocytoplasmic transport of p53 and AMPK activation. KPNA2/p53 inhibitors attenuated autophagy induced by silencing TMOD1 in AML cells. Silencing TMOD1 also inhibited tumor growth by elevating KPNA2-mediated autophagy in nude mice bearing MOLM-13 xenografts. Collectively, our data demonstrated that TMOD1 could be a novel therapeutic target for AML treatment.
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Autofagia , Proliferación Celular , Leucemia Mieloide Aguda , Ratones Desnudos , Tropomodulina , alfa Carioferinas , Humanos , Animales , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , alfa Carioferinas/genética , alfa Carioferinas/metabolismo , Tropomodulina/genética , Tropomodulina/metabolismo , Línea Celular Tumoral , Ratones , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Ratones Endogámicos BALB C , Masculino , Silenciador del Gen , Femenino , Células THP-1RESUMEN
Medium-sized lactones are important structural units, but their synthesis remains a great challenge. Herein, we report I2/CF3CO2Ag-mediated iodolactonization of allenoic acids to synthesize various 6- to 9-membered ring vinylic iodolactones in 16-89% yield. This protocol not only develops a new cyclization strategy of allenoic acids, but also provides highly functionalized medium-sized lactones containing alkene and halogen groups.
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Terpenoids are a class of structurally complex, naturally occurring compounds found predominantly in plant, animal, and microorganism secondary metabolites. Classical terpenoids typically have carbon atoms in multiples of five and follow well-defined carbon skeletons, whereas noncanonical terpenoids deviate from these patterns. These noncanonical terpenoids often result from the methyltransferase-catalyzed methylation modification of substrate units, leading to irregular carbon skeletons. In this comprehensive review, various activities and applications of these noncanonical terpenes have been summarized. Importantly, the review delves into the biosynthetic pathways of noncanonical terpenes, including those with C6, C7, C11, C12, and C16 carbon skeletons, in bacteria and fungi host. It also covers noncanonical triterpenes synthesized from non-squalene substrates and nortriterpenes in Ganoderma lucidum, providing detailed examples to elucidate the intricate biosynthetic processes involved. Finally, the review outlines the potential future applications of noncanonical terpenoids. In conclusion, the insights gathered from this review provide a reference for understanding the biosynthesis of these noncanonical terpenes and pave the way for the discovery of additional unique and novel noncanonical terpenes. KEY POINTS: â¢The activities and applications of noncanonical terpenoids are introduced. â¢The noncanonical terpenoids with irregular carbon skeletons are presented. â¢The microbial biosynthesis of noncanonical terpenoids is summarized.
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Terpenos , Triterpenos , Animales , Carbono , Metiltransferasas , Procesamiento Proteico-PostraduccionalRESUMEN
Resina Draconis is a traditional Chinese medicine, with the in-depth research, its medicinal value in anti-tumor has been revealed. Loureirin A is extracted from Resina Draconis, however, research on the anti-tumor efficacy of Loureirin A is rare. Herein, we investigated the function of Loureirin A in melanoma. Our research demonstrated that Loureirin A inhibited the proliferation of and caused G0/G1 cell cycle arrest in melanoma cells in a concentration-dependent manner. Further study showed that the melanin content and tyrosinase activity was enhanced after Loureirin A treatment, demonstrated that Loureirin A promoted melanoma cell differentiation, which was accompanied with the reduce of WNT signaling pathway. Meanwhile, we found that Loureirin A suppressed the migration and invasion of melanoma cells through the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Taken together, this study demonstrated for the first time the anti-tumor effects of Loureirin A in melanoma cells, which provided a novel therapeutic strategy against melanoma.
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Chalconas , Melanoma , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Melanoma/metabolismo , Diferenciación Celular , Vía de Señalización Wnt , Serina-Treonina Quinasas TOR/metabolismo , Proliferación Celular , Movimiento Celular , Línea Celular TumoralRESUMEN
Auxin Response Factors (ARFs) make up a plant-specific transcription factor family that mainly couples perception of the phytohormone, auxin, and gene expression programs and plays an important and multi-faceted role during plant growth and development. Lemongrass (Cymbopogon flexuosus) is a representative Cymbopogon species widely used in gardening, beverages, fragrances, traditional medicine, and heavy metal phytoremediation. Biomass yield is an important trait for several agro-economic purposes of lemongrass, such as landscaping, essential oil production, and phytoremediation. Therefore, we performed gene mining of CfARFs and identified 26 and 27 CfARF-encoding genes in each of the haplotype genomes of lemongrass, respectively. Phylogenetic and domain architecture analyses showed that CfARFs can be divided into four groups, among which groups 1, 2, and 3 correspond to activator, repressor, and ETTN-like ARFs, respectively. To identify the CfARFs that may play major roles during the growth of lemongrass plants, RNA-seq was performed on three tissues (leaf, stem, and root) and four developmental stages (3-leaf, 4-leaf, 5-leaf. and mature stages). The expression profiling of CfARFs identified several highly expressed activator and repressor CfARFs and three CfARFs (CfARF3, 18, and 35) with gradually increased levels during leaf growth. Haplotype-resolved transcriptome analysis revealed that biallelic expression dominance is frequent among CfARFs and contributes to their gene expression patterns. In addition, co-expression network analysis identified the modules enriched with CfARFs. By establishing orthologous relationships among CfARFs, sorghum ARFs, and maize ARFs, we showed that CfARFs were mainly expanded by whole-genome duplications, and that the duplicated CfARFs might have been divergent due to differential expression and variations in domains and motifs. Our work provides a detailed catalog of CfARFs in lemongrass, representing a first step toward characterizing CfARF functions, and may be useful in molecular breeding to enhance lemongrass plant growth.
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Cymbopogon , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos , Filogenia , Proteínas de Plantas , Cymbopogon/genética , Cymbopogon/metabolismo , Cymbopogon/crecimiento & desarrollo , Ácidos Indolacéticos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Desarrollo de la Planta/genética , Reguladores del Crecimiento de las Plantas/metabolismo , Perfilación de la Expresión Génica , HaplotiposRESUMEN
Among diverse protein post-translational modifications, O-GlcNAcylation, a simple but essential monosaccharide modification, plays crucial roles in cellular processes and is closely related to various diseases. Despite its ubiquity in cells, properties of low stoichiometry and reversibility are hard nuts to crack in system-wide research of O-GlcNAc. Herein, we developed a novel method employing multi-comparative thermal proteome profiling for O-GlcNAc transferase (OGT) substrate discovery. Melting curves of proteins under different treatments were profiled and compared with high reproducibility and consistency. Consequently, proteins with significantly shifted stabilities caused by OGT and uridine-5'-diphosphate N-acetylglucosamine were screened out from which new O-GlcNAcylated proteins were uncovered.
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Procesamiento Proteico-Postraduccional , Proteoma , Proteoma/metabolismo , Reproducibilidad de los Resultados , Acetilglucosamina/químicaRESUMEN
We theoretically present the waveform controls of terahertz (THz) radiations generated from homogeneous and rippled plasma within inhomogeneous external electrostatic field. The Particle-in-cell (PIC) simulations is implemented to demonstrate generation and controllability of three types of THz pulses: single frequency THz pulse in homogeneous plasma, broadband THz pulse and dual frequency THz pulse in rippled plasma. The single frequency THz pulse can be tuned via shifting the knob of electron density of homogeneous plasma. Waveform of broadband THz pulse can be regulated into an envelope-like shape by varying amplitude of electron density of rippled plasma. The two center frequencies' interval of dual frequency THz pulse can be controlled by wave numbers of density distribution of rippled plasma. This work provides a potential means to generate the dual frequency THz pulses with two harmonic frequencies (ω+Ωω, Ω=2) or incommensurate frequencies (ω+Ωω, Ω=1.7,1.8, 2.2 ).
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Central carbon metabolism (CCM), including glycolysis, tricarboxylic acid cycle and the pentose phosphate pathway, is the most fundamental metabolic process in the activities of living organisms that maintains normal cellular growth. CCM has been widely used in microbial metabolic engineering in recent years due to its unique regulatory role in cellular metabolism. Using yeast and Escherichia coli as the representative organisms, we summarized the metabolic engineering strategies on the optimization of CCM in eukaryotic and prokaryotic microbial chassis, such as the introduction of heterologous CCM metabolic pathways and the optimization of key enzymes or regulatory factors, to lay the groundwork for the future use of CCM optimization in metabolic engineering. Furthermore, the bottlenecks in the application of CCM optimization in metabolic engineering and future application prospects are summarized.
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Carbono , Ingeniería Metabólica , Carbono/metabolismo , Redes y Vías Metabólicas , Vía de Pentosa Fosfato , Ciclo del Ácido Cítrico , Escherichia coli/metabolismo , Saccharomyces cerevisiae/metabolismoRESUMEN
Hepatocellular carcinoma (HCC) is a malignant tumor with a high rate of recurrence and a poor prognosis. Here, we investigated the effect and the potential antitumor mechanism of Gamabufotalin (CS-6) against HCC. Our results show that CS-6 strikingly reduced cell viability, inhibited colony formation, and promoted apoptosis in Hep3B and Huh7 cells. In vivo, CS-6 inhibited HCC xenograft tumor growth with no toxicity to normal tissues. Mechanistically, we found that CS-6 could induce cytoprotective autophagy through the mTOR-ULK1 signaling pathway through downregulation of p62 and upregulation of LC3 II/LC3 I. Meanwhile, CS-6 activated caspase-3 and PARP mediated apoptosis, and the caspase inhibitor Z-VAD-FMK blocked the CS-6-induced cell death in HCC cells. Moreover, autophagy and apoptosis were found to have antagonistic effects in Hep3B and Huh7 cells. Both the autophagy inhibitor chloroquine (CQ) and the mTOR activator MHY1485 blocked autophagy and further enhanced CS-6-induced apoptosis. Taken together, we demonstrated for the first time that CS-6 promotes apoptosis and cytoprotective autophagy through the mTOR signaling pathway in HCC, which proposes a novel strategy for HCC therapy.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Apoptosis , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Autofagia , Línea Celular Tumoral , Proliferación CelularRESUMEN
Rare ginsenosides are the deglycosylated secondary metabolic derivatives of major ginsenosides, and they are more readily absorbed into the bloodstream and function as active substances. The traditional preparation methods hindered the potential application of these effective components. The continuous elucidation of ginsenoside biosynthesis pathways has rendered the production of rare ginsenosides using synthetic biology techniques effective for their large-scale production. Previously, only the progress in the biosynthesis and biotechnological production of major ginsenosides was highlighted. In this review, we summarized the recent advances in the identification of key enzymes involved in the biosynthetic pathways of rare ginsenosides, especially the glycosyltransferases (GTs). Then the construction of microbial chassis for the production of rare ginsenosides, mainly in Saccharomyces cerevisiae, was presented. In the future, discovery of more GTs and improving their catalytic efficiencies are essential for the metabolic engineering of rare ginsenosides. This review will give more clues and be helpful for the characterization of the biosynthesis and metabolic engineering of rare ginsenosides. KEY POINTS: ⢠The key enzymes involved in the biosynthetic pathways of rare ginsenosides are summarized. ⢠The recent progress in metabolic engineering of rare ginsenosides is presented. ⢠The discovery of glycosyltransferases is essential for the microbial production of rare ginsenosides in the future.
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Ginsenósidos , Panax , Ingeniería Metabólica , Ginsenósidos/metabolismo , Panax/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismoRESUMEN
Aging is a pressing global health issue that is linked to various diseases, such as diabetes and Alzheimer's disease. It is well known that glycation plays a pathological role in the aging process and age-related diseases. Thus, it is of great significance to discover protein glycation at an early stage for monitoring and intervention in the aging process. However, the endogenous age-related early-stage glycated proteome remains insufficiently profiled. To address this research gap, our study focuses on assessing glycated proteomics profiles in the serum of mice. We employ a robust and quantitative strategy previously developed by our team, to analyze endogenous glycated proteome in serum samples of 4 age groups of mice (10 weeks, 16 weeks, 48 weeks and 80 weeks). In total, 2959 endogenous glycated peptides corresponding to 296 serum proteins are identified from 48 runs of serum samples from 16 mice across the four age groups. By comparing these glycated peptides between adjacent age groups, we discover 49 glycated peptides from 35 proteins that show significant upregulation between the 48-week and 80-week age groups. Furthermore, we identify 10 glycated proteins (or protein groups) that are significantly upregulated only between the 48-week and 80-week age groups, including lecithin-cholesterol acyltransferase (LCAT) and apolipoprotein A-II (Apo A-II). These novel findings provide unique signatures for understanding the aging process and age-related diseases. By shedding light on the early-stage glycated proteome, our study contributes valuable insights that may have implications for future interventions and therapeutic approaches.
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Diabetes Mellitus , Proteoma , Animales , Ratones , Proteoma/metabolismo , Glicosilación , Proteinas Glicosiladas , Péptidos/metabolismoRESUMEN
Gastric cancer (GC) is one of the most common malignant tumors worldwide. Thus, the development of safe and effective therapeutic compounds for GC treatment is urgently required. Here, we aimed to examine the role of picropodophyllin (PPP), a compound extracted from the rhizome of Dysosma versipellis (Hance) M. Cheng ex Ying, on the proliferation of GC cells. Our study revealed that PPP inhibits the proliferation of GC cells in a dose-dependent manner by inducing apoptosis. Moreover, our study elucidated that PPP suppresses the growth of GC tumor xenografts with no side effects of observable toxicity. Mechanistically, PPP exerts its effects by blocking the AKT/mammalian target of rapamycin (mTOR) signaling pathway; these effects are markedly abrogated by the overexpression of constitutively active AKT. Furthermore, drug affinity responsive target stability (DARTS) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) revealed that heat shock protein 90 (HSP90) may be a potential target of PPP. Surface plasmon resonance and immunoprecipitation assay validated that PPP directly targets HSP90 and disrupts the binding of HSP90 to AKT, thereby suppressing GC cell proliferation. Thus, our study revealed that PPP may be a promising therapeutic compound for GC treatment.
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Terahertz (THz) radiations from graphene are expected to provide a powerful light source for their wide applications. However, their conversion efficiencies are limited with either long-duration or few-cycle single-color laser pulses. Here, we theoretically demonstrate that THz waves can be efficiently generated from monolayer graphene by using a long-duration two-color laser pulse at normal incidence. Our simulated results show that low-frequency THz emissions are sensitive to the phase difference between two colors, the laser intensity, and the fundamental wavelength. Their dependence on these parameters can be very well reproduced by asymmetry parameters accounting for electron populations of conduction and valence bands. On the contrary, a newly defined σ parameter including the Landau-Zener tunneling probability cannot precisely predict such dependence. Furthermore, the waveform of THz electric field driven by two-color laser pulses exhibits the typical feature of a half-cycle pulse.
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The two-color strong-field mixing in gas medium is a widely used approach to generate bright broadband terahertz (THz) radiation. Here, we present a new, to the best of our knowledge, and counterintuitive method to promote THz performance in the two-color scheme. Beyond our knowledge that the maximum THz generation occurs with two-color foci overlapped, we found that, when the foci of two-color beams are noticeably separated along the propagation axis resulting in cascading plasmas, the THz conversion efficiency is surged by one order of magnitude and the bandwidth is stretched by more than two times, achieving 10-3 conversion efficiency and >100 THz bandwidth under the condition of 800/400 nm, â¼35 fs driving lasers. With the help of the pulse propagation equation and photocurrent model, the observations can be partially understood by the compromise between THz generation and absorption due to the spatial redistribution of laser energy in cascading plasmas. The present method can be extended to a mid-infrared driving laser, and new records of THz peak power and conversion efficiency are expected.
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Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0-G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.
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Dinámicas Mitocondriales , Neoplasias Gástricas , Ratones , Animales , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Ratones Desnudos , Proteínas Quinasas/farmacología , Apoptosis , Carcinogénesis , Proliferación Celular , Línea Celular TumoralRESUMEN
The reactive oxygen species (ROS) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway play critical roles in the pathogenesis of prostate cancer by modulating cell proliferation. Picropodophyllin (PPP), an inhibitor of the insulin-like growth factor 1 receptor (IGF-1R), exerts significant antitumor effects via the PI3K/AKT signaling pathway. However, the effects of PPP on prostate cancer via ROS production and the PI3K/AKT signaling pathway remain elusive. Herein, we focused on examining the antitumor effects of PPP on DU145 and LNCaP human prostate cancer cells to determine the possible molecular mechanism. Our data indicated that the inhibitory effect of PPP on the proliferation of DU145 and LNCaP human prostate cancer cells was mediated by apoptosis induction and cell cycle blockade. Furthermore, PPP significantly influenced the expression of apoptosis-related, cell cycle, ROS production, and PI3K/AKT signaling proteins. These findings suggest that PPP can induce cell cycle arrest and apoptosis via the production of ROS and inhibition of PI3K/AKT signaling pathway, thereby suppressing the proliferation of prostate cancer cells.
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Neoplasias de la Próstata , Proteínas Proto-Oncogénicas c-akt , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Humanos , Masculino , Fosfatidilinositol 3-Quinasa , Fosfatidilinositol 3-Quinasas/metabolismo , Podofilotoxina/análogos & derivados , Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de OxígenoRESUMEN
BACKGROUND: Occupational exposure may be associated with an increased risk of developing hyperuricemia. This study sheds lights on the association between occupational exposure and hyperuricemia in steelworkers. METHOD: A nested case-control study was conducted within a cohort of workers in steel companies to explore the association between occupational exposure and hyperuricemia. The case group consisted of a total of 641 cases of hyperuricemia identified during the study period, while 641 non-hyperuricemia subjects with the same age and gender distribution were randomly selected from the cohort as the control group. RESULTS: The incidence rate of hyperuricemia among workers in the steel company was 17.30%, with an incidence density of 81.32/1,000 person-years. In comparison to the reference group, the risks of developing hyperuricemia for steelworkers undergoing ever shifts, current shifts, heat exposure, and dust exposure were 2.18 times, 1.81 times, 1.58 times and 1.34 times higher respectively. The odds ratios (ORs) and 95% confidence intervals (CIs) were 1.87(1.12-3.13) and 2.02(1.21-3.37) for the cumulative number of days of night work at 0-1,972.80 and ≥ 1,972.80 (days), respectively. Compared to the group with the cumulative heat exposure of 0 (°C/year), the ORs (95% CI) for the risk of developing hyperuricemia in the groups with the cumulative heat exposure of 0-567.83 and ≥ 567.83 (°C/year) were 1.50(1.02-2.22) and 1.64(1.11-2.43), respectively. The OR (95% CI) for the risk of developing hyperuricemia was 1.56(1.05-2.32) at the cumulative dust exposure of ≥ 30.02 (mg/m3/year) compared to that at the cumulative dust exposure of 0 (mg/m3/year). Furthermore, there was a multiplicative interaction between heat exposure and dust exposure in the development of hyperuricemia. CONCLUSION: Shift work, heat, and dust are independent risk factors for the development of hyperuricemia in steelworkers. Additionally, there is a multiplicative interaction between heat exposure and dust exposure in the development of hyperuricemia. Interventions for shift work, heat and dust may help to reduce the incidence rate of hyperuricemia and improve the health of steelworkers.