Cutting Edge: STING Induces ACLY Activation and Metabolic Adaptations in Human Macrophages through TBK1.

The 2'3'-cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of IFN genes (STING) pathway can sense infection and cellular stress by detecting cytosolic DNA. Upon ligand binding, cGAS produces the cyclic dinucleotide messenger cGAMP, which triggers its receptor STING. Active STING initiates gene transcription through the transcription factors IFN regulatory factor 3 (IRF3) and NF-κB and induces autophagy, but whether STING can cause changes in the metabolism of macrophages is unknown. In this study, we report that STING signaling activates ATP-citrate lyase (ACLY) by phosphorylation in human macrophages. Using genetic and pharmacologic perturbation, we show that STING targets ACLY via its prime downstream signaling effector TANK (TRAF family member-associated NF-κB activator)-binding kinase 1 (TBK1). We further identify that TBK1 alters cellular metabolism upon cGAMP treatment. Our results suggest that STING-mediated metabolic reprogramming adjusts the cellular response to DNA sensing in addition to transcription factor activation and autophagy induction.

Vicarious punishment of moral violations in naturalistic drama narratives predicts cortical synchronization.

Punishment of moral norm violators is instrumental for human cooperation. Yet, social and affective neuroscience research has primarily focused on second- and third-party norm enforcement, neglecting the neural architecture underlying observed (vicarious) punishment of moral wrongdoers. We used naturalistic television drama as a sampling space for observing outcomes of morally-relevant behaviors to assess how individuals cognitively process dynamically evolving moral actions and their consequences. Drawing on Affective Disposition Theory, we derived hypotheses linking character morality with viewers' neural processing of characters' rewards and punishments. We used functional magnetic resonance imaging (fMRI) to examine neural responses of 28 female participants while free-viewing 15 short story summary video clips of episodes from a popular US television soap opera. Each summary included a complete narrative structure, fully crossing main character behaviors (moral/immoral) and the consequences (reward/punishment) characters faced for their actions. Narrative engagement was examined via intersubject correlation and representational similarity analysis. Highest cortical synchronization in 9 specifically selected regions previously implicated in processing moral information was observed when characters who act immorally are punished for their actions with participants' empathy as an important moderator. The results advance our understanding of the moral brain and the role of normative considerations and character outcomes in viewers' engagement with popular narratives.

Amino-acid- and peptide-directed synthesis of chiral plasmonic gold nanoparticles.

Understanding chirality, or handedness, in molecules is important because of the enantioselectivity that is observed in many biochemical reactions 1 , and because of the recent development of chiral metamaterials with exceptional light-manipulating capabilities, such as polarization control2-4, a negative refractive index 5 and chiral sensing 6 . Chiral nanostructures have been produced using nanofabrication techniques such as lithography 7 and molecular self-assembly8-11, but large-scale and simple fabrication methods for three-dimensional chiral structures remain a challenge. In this regard, chirality transfer represents a simpler and more efficient method for controlling chiral morphology12-18. Although a few studies18,19 have described the transfer of molecular chirality into micrometre-sized helical ceramic crystals, this technique has yet to be implemented for metal nanoparticles with sizes of hundreds of nanometres. Here we develop a strategy for synthesizing chiral gold nanoparticles that involves using amino acids and peptides to control the optical activity, handedness and chiral plasmonic resonance of the nanoparticles. The key requirement for achieving such chiral structures is the formation of high-Miller-index surfaces ({hkl}, h ≠ k ≠ l ≠ 0) that are intrinsically chiral, owing to the presence of 'kink' sites20-22 in the nanoparticles during growth. The presence of chiral components at the inorganic surface of the nanoparticles and in the amino acids and peptides results in enantioselective interactions at the interface between these elements; these interactions lead to asymmetric evolution of the nanoparticles and the formation of helicoid morphologies that consist of highly twisted chiral elements. The gold nanoparticles that we grow display strong chiral plasmonic optical activity (a dis-symmetry factor of 0.2), even when dispersed randomly in solution; this observation is supported by theoretical calculations and direct visualizations of macroscopic colour transformations. We anticipate that our strategy will aid in the rational design and fabrication of three-dimensional chiral nanostructures for use in plasmonic metamaterial applications.

Chiral plasmonic sensing: From the perspective of light-matter interaction.

Molecular chirality is represented as broken mirror symmetry in the structural orientation of constituent atoms and plays a pivotal role at every scale of nature. Since the discovery of the chiroptic property of chiral molecules, the characterization of molecular chirality is important in the fields of biology, physics, and chemistry. Over the centuries, the field of optical chiral sensing was based on chiral light-matter interactions between chiral molecules and polarized light. Starting from simple optics-based sensing, the utilization of plasmonic materials that could control local chiral light-matter interactions by squeezing light into molecules successfully facilitated chiral sensing into noninvasive, ultrasensitive, and accurate detection. In this Review, the importance of plasmonic materials and their engineering in chiral sensing are discussed based on the principle of chiral light-matter interactions and the theory of optical chirality and chiral perturbation; thus, this Review can serve as a milestone for the proper design and utilization of plasmonic nanostructures for improved chiral sensing.

The Impact of COVID-19 and Exposure to Violent Media Content on Cyber Violence Victimization Among Adolescents in South Korea: National Population-Based Study.

BACKGROUND: Because of the COVID-19 pandemic and consequent stay-at-home mandates, adolescents faced isolation and a decline in mental health. With increased online activity during this period, concerns arose regarding exposure to violent media content and cyber victimization among adolescents. Yet, the precise influence of pandemic-related measures on experiences of cyber violence remains unclear. Hence, it is pertinent to investigate whether the pandemic altered the dynamics of cyber violence victimization for individuals. OBJECTIVE: This study aims to investigate the effects of COVID-19 and exposure to violent media content on cyber violence victimization among adolescents in South Korea. METHODS: We used national survey data from 2019 (n=4779) and 2020 (n=4958) to investigate the potential impact of COVID-19 on the prevalence of cyber violence among young adolescents. The data encompassed responses from elementary fourth-grade students to senior high school students, probing their exposure to violent media content, average internet use, as well as experiences of victimization and perpetration. RESULTS: The analysis revealed a noteworthy decline in cyber victimization during 2020 compared with 2019 (B=-0.12, t=-3.45, P<.001). Furthermore, being a perpetrator significantly contributed to cyber victimization (B=0.57, t=48.36, P<.001). Additionally, younger adolescents (ß=-.06, t=-6.09, P<.001), those spending more time online (ß=.18, t=13.83, P<.001), and those exposed to violent media (ß=.14, t=13.89, P<.001) were found to be more susceptible to victimization. CONCLUSIONS: Despite the widespread belief that cyber violence among adolescents surged during COVID-19 due to increased online activity, the study findings counter this assumption. Surprisingly, COVID-19 did not exacerbate cyber victimization; rather, it decreased it. Given the strong correlation between cyber victimization and offline victimization, our attention should be directed toward implementing real-life interventions aimed at curbing violence originating from in-person violence at school.

CRISPR/Cas9-Mediated HY5 Gene Editing Reduces Growth Inhibition in Chinese Cabbage (Brassica rapa) under ER Stress.

Various stresses can affect the quality and yield of crops, including vegetables. In this study, CRISPR/Cas9 technology was employed to examine the role of the ELONGATED HYPOCOTYL 5 (HY5) gene in influencing the growth of Chinese cabbage (Brassica rapa). Single guide RNAs (sgRNAs) were designed to target the HY5 gene, and deep-sequencing analysis confirmed the induction of mutations in the bZIP domain of the gene. To investigate the response of Chinese cabbage to endoplasmic reticulum (ER) stress, plants were treated with tunicamycin (TM). Both wild-type and hy5 mutant plants showed increased growth inhibition with increasing TM concentration. However, the hy5 mutant plants displayed less severe growth inhibition compared to the wild type. Using nitroblue tetrazolium (NBT) and 3,3'-diaminobenzidine (DAB) staining methods, we determined the amount of reactive oxygen species (ROS) produced under ER stress conditions, and found that the hy5 mutant plants generated lower levels of ROS compared to the wild type. Under ER stress conditions, the hy5 mutant plants exhibited lower expression levels of UPR- and cell death-related genes than the wild type. These results indicate that CRISPR/Cas9-mediated editing of the HY5 gene can mitigate growth inhibition in Chinese cabbage under stresses, improving the quality and yield of crops.

Pregnancy loss and Income in the Republic of Korea using National Health Insurance Service Data, 2008-2014.

BACKGROUND: Although unintentional pregnancy loss is common, national representative statistics are lacking in high-income East Asian countries undergoing rapid demographic changes. It is necessary to confirm the income inequality of pregnancy loss even in universal national health insurance. METHOD: Using National Health Insurance Service data between 2008 and 2014, the annual prevalence of pregnancy loss was enumerated, and differences in pregnancy loss according to age and income levels were assessed by multivariable Poisson regression. Joint-point regression was used to examine the trend of pregnancy loss. RESULT: On average, there was a 15.0% annual pregnancy loss among 3,941,020 pregnancy cases from 2008 to 2014. Pregnancy loss inequality increased stepwise with income levels except for the highest income group. After adjusting for income levels, the annual percent change of age-standardized prevalence significantly increased by 2.6% every year since 2011. CONCLUSION: Even in high-income countries with universal national health insurance, income inequality in pregnancy loss is observed. Further appraisal is needed to explain the increasing trend of pregnancy loss between 2011 and 2014 even after adjusting income.

Plasma Aldo-Keto Reductase Family 1 Member B10 as a Biomarker Performs Well in the Diagnosis of Nonalcoholic Steatohepatitis and Fibrosis.

We found several blood biomarkers through computational secretome analyses, including aldo-keto reductase family 1 member B10 (AKR1B10), which reflected the progression of nonalcoholic fatty liver disease (NAFLD). After confirming that hepatic AKR1B10 reflected the progression of NAFLD in a subgroup with NAFLD, we evaluated the diagnostic accuracy of plasma AKR1B10 and other biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) and fibrosis in replication cohort. We enrolled healthy control subjects and patients with biopsy-proven NAFLD (n = 102) and evaluated the performance of various diagnostic markers. Plasma AKR1B10 performed well in the diagnosis of NASH with an area under the receiver operating characteristic (AUROC) curve of 0.834 and a cutoff value of 1078.2 pg/mL, as well as advanced fibrosis (AUROC curve value of 0.914 and cutoff level 1078.2 pg/mL), with further improvement in combination with C3. When we monitored a subgroup of obese patients who underwent bariatric surgery (n = 35), plasma AKR1B10 decreased dramatically, and 40.0% of patients with NASH at baseline showed a decrease in plasma AKR1B10 levels to below the cutoff level after the surgery. In an independent validation study, we proved that plasma AKR1B10 was a specific biomarker of NAFLD progression across varying degrees of renal dysfunction. Despite perfect correlation between plasma and serum levels of AKR1B10 in paired sample analysis, its serum level was 1.4-fold higher than that in plasma. Plasma AKR1B10 alone and in combination with C3 could be a useful noninvasive biomarker for the diagnosis of NASH and hepatic fibrosis.

Autophagic defects observed in fibroblasts from a patient with ß-propeller protein-associated neurodegeneration.

Beta-propeller protein-associated neurodegeneration (BPAN) is associated with mutations in the autophagy gene WDR45. The aim of this study was to demonstrate autophagic defects in a patient with BPAN. We assayed autophagic markers using western blot analysis and immunocytochemistry and applied transmission electron microscopy (TEM) to visualize the autophagic structures in fibroblasts from a 7-year-old Korean female with WDR45 splice-site mutation (c.977-1G>A; NM_007075.3). The protein and mRNA expression levels of WDR45 gene were decreased in the patient-derived fibroblasts. The amount of increase in LC3-II upon treatment with an autophagy inducer and inhibitor was reduced in mutant cells compared to control cells, suggesting decreased autophagic flux. TEM showed the accumulation of large vacuoles in mutant cells with a decrease of autophagosomes. Our study demonstrated that the WDR45 mutation in this patient impaired autophagy and provided additional insight into ultrastructural changes of autophagic structures.

Increased risk of suicide after occupational injury in Korea.

OBJECTIVES: This study sought to investigate the association between occupational injury and subsequent risk of suicide in Korea. METHODS: We linked compensation data for 775 537 workers injured at work during 2003-2014 with National Death Registry through 2015. Suicide among injured workers was compared with the economically active population in Korea separately for men and women by calculating SMRs, with 95% CIs. RESULTS: Injured workers showed higher mortality from suicide for both men (SMR=2.22, 95% CI 2.14 to 2.31) and women (SMR=2.11, 95% CI 1.81 to 2.45) compared with the economically active population in Korea. CONCLUSIONS: Occupational injuries are associated with substantially elevated suicide risk in Korea. The results suggest the importance of social policies to protect and support injured workers as well as intensifying efforts to prevent workplace injuries.

Iron Accumulation and Changes in Cellular Organelles in WDR45 Mutant Fibroblasts.

Iron overload in the brain, defined as excess stores of iron, is known to be associated with neurological disorders. In neurodegeneration accompanied by brain iron accumulation, we reported a specific point mutation, c.974-1G>A in WD Repeat Domain 45 (WDR45), showing iron accumulation in the brain, and autophagy defects in the fibroblasts. In this study, we investigated whether fibroblasts with mutated WDR45 accumulated iron, and other effects on cellular organelles. We first identified the main location of iron accumulation in the mutant fibroblasts and then investigated the effects of this accumulation on cellular organelles, including lipid droplets, mitochondria and lysosomes. Ultrastructure analysis using transmission electron microscopy (TEM) and confocal microscopy showed structural changes in the organelles. Increased numbers of lipid droplets, fragmented mitochondria and increased numbers of lysosomal vesicles with functional disorder due to WDR45 deficiency were observed. Based on correlative light and electron microscopy (CLEM) findings, most of the iron accumulation was noted in the lysosomal vesicles. These changes were associated with defects in autophagy and defective protein and organelle turnover. Gene expression profiling analysis also showed remarkable changes in lipid metabolism, mitochondrial function, and autophagy-related genes. These data suggested that functional and structural changes resulted in impaired lipid metabolism, mitochondrial disorder, and unbalanced autophagy fluxes, caused by iron overload.

Genome-Wide Analysis of MYB10 Transcription Factor in Fragaria and Identification of QTLs Associated with Fruit Color in Octoploid Strawberry.

The genus Fragaria encompass fruits with diverse colors influenced by the distribution and accumulation of anthocyanin. Particularly, the fruit colors of strawberries with different ploidy levels are determined by expression and natural variations in the vital structural and regulatory genes involved in the anthocyanin pathway. Among the regulatory genes, MYB10 transcription factor is crucial for the expression of structural genes in the anthocyanin pathway. In the present study, we performed a genome wide investigation of MYB10 in the diploid and octoploid Fragaria species. Further, we identified seven quantitative trait loci (QTLs) associated with fruit color in octoploid strawberry. In addition, we predicted 20 candidate genes primarily influencing the fruit color based on the QTL results and transcriptome analysis of fruit skin and flesh tissues of light pink, red, and dark red strawberries. Moreover, the computational and transcriptome analysis of MYB10 in octoploid strawberry suggests that the difference in fruit colors could be predominantly influenced by the expression of MYB10 from the F. iinumae subgenome. The outcomes of the present endeavor will provide a platform for the understanding and tailoring of anthocyanin pathway in strawberry for the production of fruits with aesthetic colors.

Versatile Nutraceutical Potentials of Watermelon-A Modest Fruit Loaded with Pharmaceutically Valuable Phytochemicals.

Watermelon (Citrulus lantus) is an important horticultural crop which belongs to the Curcubitaceae family. The nutraceutical potential of watermelon has been illustrated by several researchers, which makes it a better choice of functional food. Watermelon has been used to treat various ailments, such as cardio-vascular diseases, aging related ailments, obesity, diabetes, ulcers, and various types of cancers. The medicinal properties of watermelon are attributed by the presence of important phytochemicals with pharmaceutical values such as lycopene, citrulline, and other polyphenolic compounds. Watermelon acts as vital source of l-citrulline, a neutral-alpha amino acid which is the precursor of l-arginine, an essential amino acid necessary for protein synthesis. Supplementation of l-citrulline and lycopene displayed numerous health benefits in in vitro and in vivo studies. Similarly, the dietary intake of watermelon has proven benefits as functional food in humans for weight management. Apart from the fruits, the extracts prepared from the seeds, sprouts, and leaves also evidenced medicinal properties. The present review provides a comprehensive overview of benefits of watermelon for the treatment of various ailments.

γ-Glutamylcysteine- and Cysteinylglycine-Directed Growth of Chiral Gold Nanoparticles and their Crystallographic Analysis.

Chiral optical metamaterials with delicate structures are in high demand in various fields because of their strong light-matter interactions. Recently, a scalable strategy for the synthesis of chiral plasmonic nanoparticles (NPs) using amino acids and peptides has been reported. Reported herein, 3D chiral gold NPs were synthesized using dipeptide γ-Glu-Cys and Cys-Gly and analyzed crystallographically. The γ-Glu-Cys-directed NPs present a cube-like outline with a protruding chiral wing. In comparison, the NPs synthesized with Cys-Gly exhibited a rhombic dodecahedron-like outline with curved edges and elliptical cavities on each face. Morphology analysis of intermediates indicated that γ-Glu-Cys generated an intermediate concave hexoctahedron morphology, while Cys-Gly formed a concave rhombic dodecahedron. NPs synthesized with Cys-Gly are named 432 helicoid V because of their unique morphology and growth pathway.

Size-controllable and uniform gold bumpy nanocubes for single-particle-level surface-enhanced Raman scattering sensitivity.

Gold nanocubes modified to form roughened structures, namely, gold bumpy nanocubes (Au BNCs), with very strong and uniform single-particle surface-enhanced Raman scattering (SERS) intensity were developed. The Au BNCs were synthesized by controlled regrowth, competing with 4-aminothiophenol during gold nanocube growth. Under controlled conditions, Au BNCs of various sizes were successfully generated while maintaining a cubic outline. As the bumpy surfaces of the Au BNCs increased the number of hot spots on a single cubic nanoparticle, these nanoparticles exhibited 15-times stronger SERS than normal cubic nanoparticles. We expect that this unique nanostructure will be applicable in versatile fields as an ultrasensitive SERS nanoprobe or nanoantenna owing to its cubic outline and high uniformity, as well as the ease of particle size adjustment.

Epigallocatechin-3-Gallate Prevents Acute Gout by Suppressing NLRP3 Inflammasome Activation and Mitochondrial DNA Synthesis.

Gout is a chronic inflammatory disease evoked by the deposition of monosodium urate (MSU) crystals in joint tissues. The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome is responsible for the gout inflammatory symptoms induced by MSU crystals. We investigated whether epigallocatechin-3-gallate (EGCG) suppresses the activation of the NLRP3 inflammasome, thereby effectively preventing gouty inflammation. EGCG blocked MSU crystal-induced production of caspase-1(p10) and interleukin-1ß in primary mouse macrophages, indicating its suppressive effect on the NLRP3 inflammasome. In an acute gout mouse model, oral administration of EGCG to mice effectively alleviated gout inflammatory symptoms in mouse foot tissue injected with MSU crystals. The in vivo suppressive effects of EGCG correlated well with the suppression of the NLRP3 inflammasome in mouse foot tissue. EGCG inhibited the de novo synthesis of mitochondrial DNA as well as the production of reactive oxygen species in primary mouse macrophages, contributing to the suppression of the NLRP3 inflammasome. These results show that EGCG suppresses the activation of the NLRP3 inflammasome in macrophages via the blockade of mitochondrial DNA synthesis, contributing to the prevention of gouty inflammation. The inhibitory effects of EGCG on the NLRP3 inflammasome make EGCG a promising therapeutic option for NLRP3-dependent diseases such as gout.

Anti-obesity potential of Glycyrrhiza uralensis and licochalcone A through induction of adipocyte browning.

The main function of brown adipose tissue is to dissipate surplus caloric intake into heat energy by thermogenesis, increasing energy expenditure. Inducible brown adipocytes can develop within white adipose tissue (WAT) through a process referred to as browning. Browning of white fat represents a promising strategy for treatment of obesity and the related complications. We investigated whether Glycyrrhiza uralensis and its ingredients modulated adipogenesis through adipocyte browning using 3T3-L1 adipocytes and a high-fat diet (HFD)-induced obesity mice model. Amongst extracts and fractions of G. uralensis, methyl dichloride (MeCl2) fraction was the most effective to induce expression of uncoupling protein 1 (UCP1), a fat browning marker, in 3T3-L1 adipocytes. Ingredients of G. uralensis such as licochalcone A (LicoA), isoliquiritigenin, and liquiritigenin induced UCP1 expression in 3T3-L1 adipocytes. After inducing obesity in mice by 6-week HFD, MeCl2 fraction of G. uralensis or LicoA was intraperitoneally administered for additional 19 days. MeCl2 fraction or LicoA significantly reduced body weight gain and inguinal fat pad weights. Furthermore, MeCl2 fraction or LicoA improved metabolic disorders induced by HFD as the treatments decreased serum levels of glucose and cholesterol, and blocked insulin resistance. MeCl2 fraction or LicoA enhanced expression of brown fat markers such as UCP1, PRDM16, and PGC-1α and increased brown fat phenotype population in inguinal WAT of HFD-fed mice. Our results demonstrate that G. uralensis and LicoA are effective to reduce obesity and to recover metabolic homeostasis by inducing the brown fat phenotype.

Suppression of NLRP3 inflammasome by oral treatment with sulforaphane alleviates acute gouty inflammation.

Objective: The aetiology of gout is closely linked to the deposition of monosodium uric acid (MSU) crystals and the consequent activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we investigated whether oral administration of an NLRP3 inhibitor would be effective to attenuate the symptoms of gout. Methods: The effects of oral administration with sulforaphane (SFN) were examined in two mouse models of acute gout induced by injection of MSU crystals into footpads or air pouch. The production of caspase-1 (p10) and IL-1ß was examined by immunoblotting and ELISA as hallmarks of NLRP3 inflammasome activation. Results: Oral administration of SFN attenuated MSU crystal-induced swelling and neutrophil recruitment in a mouse foot acute gout model, correlating with the suppression of the NLRP3 inflammasome activation in foot tissues. Consistently, oral administration of SFN blocked MSU-crystal-induced activation of the NLRP3 inflammasome in a mouse air pouch gout model. SFN suppressed NLRP3 inflammasome activation induced by MSU crystals, adenosine triphosphate and nigericin but not by poly(dA:dT) in primary mouse macrophages, independent of the reactive oxygen species pathway. SFN inhibited ligand-independent activation of the NLRP3 inflammasome, suggesting that SFN may act directly on the NLRP3 inflammasome complex. Conclusion: Oral administration of SFN effectively alleviated acute gouty inflammation by suppression of the NLRP3 inflammasome. Our results provide a novel strategy in which oral treatment with SFN may be beneficial in preventing acute attacks of gout.

Licochalcone A attenuates acne symptoms mediated by suppression of NLRP3 inflammasome.

Activation of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome by Propionibacterium acnes (P. acnes) is critical for inducing inflammation and aggravating the development of acne lesions. We searched for available small-molecule inhibitors of the NLRP3 inflammasome that could be topically administered for the treatment of acne. We found that licochalcone A, a chalconoid isolated from the root of Glycyrrhiza inflate, was an effective inhibitor for P. acnes-induced NLRP3 inflammasome activation. Licochalcone A blocked P. acnes-induced production of caspase-1(p10) and IL-1ß in primary mouse macrophages and human SZ95 sebocytes, indicating the suppression of NLRP3 inflammasome. Licochalcone A suppressed P. acnes-induced ASC speck formation and mitochondrial reactive oxygen species. Topical application of licochalcone A to mouse ear skin attenuated P. acnes-induced skin inflammation as shown by histological assessment, ear thickness measurement, and inflammatory gene expression. Licochalcone A reduced caspase-1 activity and IL-1ß production in mouse ear injected with P. acnes. This study demonstrated that licochalcone A is effective in the control of P. acnes-induced skin inflammation as an efficient inhibitor for NLRP3 inflammasome. Our study provides a new paradigm for the development of anti-acne therapy via targeting NLRP3 inflammasome.

Mortality rates by occupation in Korea: a nationwide, 13-year follow-up study.

OBJECTIVE: The present study sought to identify inequalities in cause-specific mortality across different occupational groups in Korea. METHODS: The cohort included Korean workers enrolled in the national employment insurance programme between 1995 and 2000. Mortality was determined by matching death between 1995 and 2009 according to a nationwide registry of the Korea National Statistical Office. The cohort was divided into nine occupational groups according to the Korean Standard Occupational Classification (KSOC). Age-standardised mortality rates of each subcohort were calculated. RESULTS: The highest age-standardised mortality rate was identified in KSOC 6 (agricultural, forestry and fishery workers; male (M): 563.0 per 100 000, female (F): 206.0 per 100 000), followed by KSOC 9 (elementary occupations; M: 499.0, F: 163.4) and KSOC 8 (plant, machine operators and assemblers; M: 380.3, F: 157.8). The lowest rate occurred in KSOC 2 (professionals and related workers; M: 209.1, F: 93.3). Differences in mortality rates between KSOC 2 and KSOC 9 (M: 289.9, F: 70.1) and the rate ratio of KSCO9 to KSCO2 (M: 2.39, F: 1.75) were higher in men. The most prominent mortality rate difference was observed in external causes of death (M: 96.9, F: 21.6) and liver disease in men (38.3 per 100 000). Mental disease showed the highest rate ratio (M: 6.31, F: 13.00). CONCLUSIONS: Substantial differences in mortality rates by occupation were identified. Main causes of death were injury, suicide and male liver disease. Development of policies to support occupations linked with a lower socioeconomic position should be prioritised.