Bacteria-derived extracellular vesicles: endogenous roles, therapeutic potentials and their biomimetics for the treatment and prevention of sepsis.

Sepsis is one of the medical conditions with a high mortality rate and lacks specific treatment despite several years of extensive research. Bacterial extracellular vesicles (bEVs) are emerging as a focal target in the pathophysiology and treatment of sepsis. Extracellular vesicles (EVs) derived from pathogenic microorganisms carry pathogenic factors such as carbohydrates, proteins, lipids, nucleic acids, and virulence factors and are regarded as "long-range weapons" to trigger an inflammatory response. In particular, the small size of bEVs can cross the blood-brain and placental barriers that are difficult for pathogens to cross, deliver pathogenic agents to host cells, activate the host immune system, and possibly accelerate the bacterial infection process and subsequent sepsis. Over the years, research into host-derived EVs has increased, leading to breakthroughs in cancer and sepsis treatments. However, related approaches to the role and use of bacterial-derived EVs are still rare in the treatment of sepsis. Herein, this review looked at the dual nature of bEVs in sepsis by highlighting their inherent functions and emphasizing their therapeutic characteristics and potential. Various biomimetics of bEVs for the treatment and prevention of sepsis have also been reviewed. Finally, the latest progress and various obstacles in the clinical application of bEVs have been highlighted.

Leaf nitrogen and phosphorus stoichiometry of the halophytes across China.

Halophytes play a crucial role in the ecological restoration of saline and alkaline land and hold promising benefits to food security in China. Although a variety of aspects of halophytes have been extensively addressed, there is still a lack of overall understanding of the leaf nitrogen (N) and phosphorus (P) stoichiometric characteristics, especially at a national scale. We compiled a national dataset of 311 observations from 113 sampling sites across China to explore the changing trends and influencing factors on leaf N and P concentrations, and N:P ratio of halophytes. The results showed that leaf N concentration decreased significantly with increasing latitude (LAT), which was mainly driven by the mean annual temperature (MAT) and mean annual precipitation (MAP). The leaf P concentration increased remarkably with increasing longitude (LON), which was induced by the variation in soil total P (TP) content. The leaf N:P ratio increased as LAT increased and LON decreased, which was potentially regulated by the MAT, MAP, and soil TP content. The scaling exponents of the N-P relationship differed significantly among halophyte types and were 0.40, 0.87, and 1.39 for euhalophyte, pseudohalophyte, and recretohalophyte, respectively. The leaf N concentration exhibited significant differences among ecosystem types and halophyte types, whereas the leaf P concentration and N:P ratio remained relatively stable. In summary, the leaf N concentration and N-P scaling exponent might be the classification criteria for halophyte types from the perspective of plant nutrient resource allocation. Moreover, this study characterized the spatial distribution and allocation strategy of leaf N and P stoichiometry in halophytes by data integration analysis, providing the basic information for nutrient management in the processes of the future domestication and introduction of halophytes.

Classification of subtypes and identification of dysregulated genes in sepsis.

Background: Sepsis is a clinical syndrome with high mortality. Subtype identification in sepsis is meaningful for improving the diagnosis and treatment of patients. The purpose of this research was to identify subtypes of sepsis using RNA-seq datasets and further explore key genes that were deregulated during the development of sepsis. Methods: The datasets GSE95233 and GSE13904 were obtained from the Gene Expression Omnibus database. Differential analysis of the gene expression matrix was performed between sepsis patients and healthy controls. Intersection analysis of differentially expressed genes was applied to identify common differentially expressed genes for enrichment analysis and gene set variation analysis. Obvious differential pathways between sepsis patients and healthy controls were identified, as were developmental stages during sepsis. Then, key dysregulated genes were revealed by short time-series analysis and the least absolute shrinkage and selection operator model. In addition, the MCPcounter package was used to assess infiltrating immunocytes. Finally, the dysregulated genes identified were verified using 69 clinical samples. Results: A total of 898 common differentially expressed genes were obtained, which were chiefly related to increased metabolic responses and decreased immune responses. The two differential pathways (angiogenesis and myc targets v2) were screened on the basis of gene set variation analysis scores. Four subgroups were identified according to median expression of angiogenesis and myc target v2 genes: normal, myc target v2, mixed-quiescent, and angiogenesis. The genes CHPT1, CPEB4, DNAJC3, MAFG, NARF, SNX3, S100A9, S100A12, and METTL9 were recognized as being progressively dysregulated in sepsis. Furthermore, most types of immune cells showed low infiltration in sepsis patients and had a significant correlation with the key genes. Importantly, all nine key genes were highly expressed in sepsis patients. Conclusion: This study revealed novel insight into sepsis subtypes and identified nine dysregulated genes associated with immune status in the development of sepsis. This study provides potential molecular targets for the diagnosis and treatment of sepsis.

[Positive effects of Xuebijing injection on intestinal microbiota and metabolite spectrum in septic rats].

OBJECTIVE: To explore the effect of Xuebijing injection on inflammation in sepsis by regulating intestinal microbiota and its metabolites. METHODS: A total of 45 male Sprague-Dawley (SD) rats were randomly divided into Sham operation group (Sham group), cecal ligation and perforation (CLP) induced sepsis group (CLP group), and Xuebijing intervention group (XBJ group, 4 mL/kg Xuebijing injection was injected intraperitoneally at 1 hour after CLP), with 15 rats in each group. The survival of rats was observed at 24 hours after operation and sacrificed. Feces were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) analysis. RESULTS: At 24 hours after operation, all rats in the Sham group survived, the mortality of rats in the XBJ group was lower than that in the CLP group [47% (7/15) vs. 60% (9/15), P > 0.05]. Compared with the Sham group, the diversity of gut microbiota in the CLP group decreased, the dominant flora changed, and the abundance of inflammation-related flora increased. Xuebijing improved the changes in gut microbiota caused by sepsis, and α diversity showed an increasing trend (Ace index: 406.0±22.5 vs. 363.2±38.2, Chao1 index: 409.7±21.8 vs. 362.4±42.5, both P > 0.05). Restrictive constrained principal coordinate analysis (cPCoA) showed a high similarity in gut microbiota among the same group of rats. The CLP group was dominated by Bacteroidetes, while the Sham and XBJ groups were dominated by Firmicutes. In addition, compared with the CLP group, Xuebijing treatment increased the abundance of beneficial bacteria in septic rats, such as Verrucomicrobia, Akkermansia and Lactobacillus. LC-MS and orthogonal partial least squares discriminant analysis (OPLS-DA) showed that there were 12 main differential metabolites among the three groups, and there were certain correlations between these metabolites, which were related to amino acid and lipid metabolism. Correlation analysis showed a significant correlation between changes in metabolites and microbial communities. CONCLUSIONS: Xuebijing can improve the survival rate of septic rats, regulate the composition of intestinal flora and related metabolites, which provides a new pathophysiological mechanism for Xuebijing in the treatment of sepsis.

InferLoop: leveraging single-cell chromatin accessibility for the signal of chromatin loop.

Deciphering cell-type-specific 3D structures of chromatin is challenging. Here, we present InferLoop, a novel method for inferring the strength of chromatin interaction using single-cell chromatin accessibility data. The workflow of InferLoop is, first, to conduct signal enhancement by grouping nearby cells into bins, and then, for each bin, leverage accessibility signals for loop signals using a newly constructed metric that is similar to the perturbation of the Pearson correlation coefficient. In this study, we have described three application scenarios of InferLoop, including the inference of cell-type-specific loop signals, the prediction of gene expression levels and the interpretation of intergenic loci. The effectiveness and superiority of InferLoop over other methods in those three scenarios are rigorously validated by using the single-cell 3D genome structure data of human brain cortex and human blood, the single-cell multi-omics data of human blood and mouse brain cortex, and the intergenic loci in the GWAS Catalog database as well as the GTEx database, respectively. In addition, InferLoop can be applied to predict loop signals of individual spots using the spatial chromatin accessibility data of mouse embryo. InferLoop is available at https://github.com/jumphone/inferloop.

Effects of Long-Term Fertilization and Stand Age on Root Nutrient Acquisition and Leaf Nutrient Resorption of Metasequoia glyptostroboides.

The plant nutrient acquisition strategies are diverse, such as root nutrient acquisition and leaf nutrient resorption, playing important roles in driving soil processes, vegetation performance as well as ecosystem nutrient cycling. However, it is still in a debate whether there is a synergy or tradeoff between above- and below-ground nutrient acquisition strategy under nitrogen (N) and phosphorus (P) addition, or with stand age. Herein, this study investigated the responses of root-soil accumulation factor (RSAF) and leaf nutrient resorption efficiency (NuRE) to long-term N and P fertilization, and further explored the trade-off between them in Metasequoia glyptostroboides plantations with different stand age. Results showed that under N fertilization in young plantations, leaf N resorption efficiency (NRE) increased, and root-soil accumulation factor for P (RSAF-P) decreased. For young forests under P fertilization, the NRE increased whereas RSAF-P decreased. For middle-aged forests under P fertilization, the NRE and leaf P resorption efficiency (PRE) increased and the RSAF-P decreased. Under P fertilization in young and middle-aged plantations, PRE had a significant positive correlation with RSAF-P. Under N fertilization in young plantations, NRE was significantly positive correlated with root-soil accumulation factor for N (RSAF-N). The covariance-based structural equation modeling (CB-SEM) analysis indicated that stand age had positive effects on PRE whether under N or P fertilization, as well as on RSAF-P under N fertilization, whereas had no effects on the NRE or RSAF-N. Overall, our results can shed light on the nutrient acquisition strategies of M. glyptostroboides plantations under future environmental changes and the results could be applied to the nutrient management practices.

Transcription factor HESX1 enhances mesendodermal commitment of human embryonic stem cells by modulating ERK1/2 signaling.

Transcription factors are key determinants of lineage commitment during mammalian development. However, the function and molecular mechanism for the transcription factors in the formation of three primary germ layers during human embryonic development are not fully elucidated. Here, we report that homeobox-containing transcription factor HESX1 plays a critical role in mesendodermal (ME) commitment of human embryonic stem cells (hESCs). Our results show that expression of HESX1 in hESCs is regulated by OCT4 and NANOG, and that its expression level changes with hESC differentiation. We find that knockdown of HESX1 does not disrupt the undifferentiated state of hESCs, in terms of cell morphology and expression levels of pluripotency-associated genes. However, HESX1 deficiency in hESCs impairs their ME commitment, whereas forced expression of HESX1 significantly enhances ME marker expression during ME commitment. Interestingly, HESX1 knockdown in hESCs represses ERK1/2 signaling activated by ME induction, while overexpression of HESX1 markedly enhances ERK1/2 activity during ME commitment of hESCs. Of note, MEK inhibitor PD0325901 weakens or even eliminates HESX1 overexpression-mediated promotive effects on ME induction in a dosage-dependent manner. Together, this study identifies a novel role of HESX1 in hESC commitment to ME cells and establishes the functional link between a transcription factor and lineage-associated signaling. These findings would help to better understand early human development and develop more efficient protocols to induce hESC differentiation to desired lineages.

Identification of metabolomics-based prognostic prediction models for ICU septic patients.

Sepsis-related global mortality remains unacceptably high in intensive care units. Identifying the various molecular processes between survival and death in septic patients may assist in better treatment. Accurate prognostic evaluation of sepsis is an essentially unmet need. This study analyzed the metabolite changes in plasma between healthy controls and septic patients, as well as between survival and dead septic patients using liquid chromatography/mass spectrometry. Univariate and multivariate analyses were applied to identify differential metabolites. The differential metabolites and clinical indicators within 24 h after sepsis diagnosis were run through multivariate logistic regression models to determine the 28-day, hospital, and 90-day septic mortality prediction models. The results suggested markedly changed amino acids metabolism in septic patients compared to healthy controls; 10, 4, and 22 primary differential metabolites related to amino acid and fatty acid metabolisms were identified in the survival and death groups at 28-day, hospital, and 90-day, respectively. Further, we found that model 1 (indoleacetic acid, 3-methylene-indolenine, heart rate, respiratory support, and application of pressure drugs), model 2 (lymphocyte count, alkaline phosphatase, SOFA, and L-alpha-amino-1H-pyrrole-1-hexanoic acid), and model 3 (dopamine, delta-12-prostaglandin J2, heart rate, respiratory support, and application of pressure drugs) could predict 28-day, hospital, and 90-day mortality of sepsis with a sensitivity of 75.51%, 73.58%, and 83.33%, specificity of 78.72%, 72.09%, and 78.57%, and the area under the receiver operating characteristic curve of 0.881, 0.830, 0.886, respectively. Thus, this research presents three multiple-biomarker-based prognostic models for 28-day, hospital, and 90-day mortality septic patients and could be used to guide sepsis treatment.

Understanding Responses of Soil Microbiome to the Nitrogen and Phosphorus Addition in Metasequoia glyptostroboides Plantations of Different Ages.

Nitrogen (N) and phosphorus (P) have significant effects on soil microbial community diversity, composition, and function. Also, trees of different life stages have different fertilization requirements. In this study, we designed three N additions and three P levels (5 years of experimental treatment) at two Metasequoia glyptostroboides plantations of different ages (young, 6 years old; middle mature, 24 years old) to understand how different addition levels of N and P affect the soil microbiome. Here, the N fertilization of M. glyptostroboides plantation land (5 years of experimental treatment) significantly enriched microbes (e.g., Lysobacter, Luteimonas, and Rhodanobacter) involved in nitrification, denitrification, and P-starvation response regulation, which might further lead to the decreasing in alpha diversity (especially in 6YMP soil). The P addition could impact the genes involved in inorganic P-solubilization and organic P-mineralization by increasing soil AP and TP. Moreover, the functional differences in the soil microbiomes were identified between the 6YMP and 24YMP soil. This study provides valuable information that improves our understanding on the effects of N and P input on the belowground soil microbial community and functional characteristics in plantations of different stand ages.

Flavonoid 3'-hydroxylase of Camellia nitidissima Chi. promotes the synthesis of polyphenols better than flavonoids.

Camellia nitidissima Chi. is an ornamental plant of the genus Camellia L. Its flowers contain a lot of flavonoids and polyphenols. Flavonoid 3'-hydroxylase (F3'H) plays an important role in the synthesis of flavonoids, polyphenols and anthocyanins. We used PCR amplification, quantitative PCR, High-performance liquid chromatography, subcellular localization, and agrobacterium-mediated leaf disk method to study the the function of CnF3'H. The full length of CnF3'H was 1859 bp (GenBank code: HQ290518.1), with an open reading frame of 1577 bp, and encoded 518 amino acid. A phylogenetic tree analysis showed that CnF3'H was closely related to Camellia sinensis L. and C. sinensis cultivar Zhonghuang. CnF3'H was expressed in flowers, leaves, fruits, sepals, petals and stamens of C. nitidissima, and during the flowering process the expression level in flower decreased initially and then increased. CnF3'H expression was significantly positive correlated with polyphenol contents in C. nitidissima. A CnF3'H-EGFP expression vector was constructed to do the subcellular localization, we found that CnF3'H was obviously localized in the nuclear envelope and cytomembrane. In transgenic tobacco flowers, the total polyphenol content and various polyphenol constituents were significantly increased with high CnF3'H expression level, while total flavonoid contents and some flavonol constituents were increased slightly. These findings suggest that CnF3'H promotes the synthesis of polyphenols better than flavonoids.

Functional Diversification of the Dihydroflavonol 4-Reductase from Camellia nitidissima Chi. in the Control of Polyphenol Biosynthesis.

Plant secondary metabolism is complex in its diverse chemical composition and dynamic regulation of biosynthesis. How the functional diversification of enzymes contributes to the diversity is largely unknown. In the flavonoids pathway, dihydroflavonol 4-reductase (DFR) is a key enzyme mediating dihydroflavanol into anthocyanins biosynthesis. Here, the DFR homolog was identified from Camellia nitidissima Chi. (CnDFR) which is a unique species of the genus Camellia with golden yellow petals. Sequence analysis showed that CnDFR possessed not only conserved catalytic domains, but also some amino acids peculiar to Camellia species. Gene expression analysis revealed that CnDFR was expressed in all tissues and the expression of CnDFR was positively correlated with polyphenols but negatively with yellow coloration. The subcellular localization of CnDFR by the tobacco infiltration assay showed a likely dual localization in the nucleus and cell membrane. Furthermore, overexpression transgenic lines were generated in tobacco to understand the molecular function of CnDFR. The analyses of metabolites suggested that ectopic expression of CnDFR enhanced the biosynthesis of polyphenols, while no accumulation of anthocyanins was detected. These results indicate a functional diversification of the reductase activities in Camellia plants and provide molecular insights into the regulation of floral color.

Arginine infusion rescues ovarian follicular development in feed-restricted Hu sheep during the luteal phase.

The aim of this study was to investigate the molecular mechanisms of arginine (Arg) on follicular development of acute feed-restricted ewes during the luteal phase. From day 6 of the estrous cycle, 24 multiparous Hu sheep were randomly assigned into three groups: control group (a maintenance diet; n = 6), feed restriction group (0.5 maintenance diet, saline infusion; n = 9) and Arg treatment group (0.5 maintenance diet, infusion with 155 µmol of Arg-HCl/kg body weight; n = 9). The intravenous administrations were performed three times per day from day 6 to day 15 of the estrous cycle. At the end of treatment, the hypothalamus and pituitary were collected, as well as the follicular fluid (FF) and granulose cells (GCs) in the ≥2.5 mm follicles. The transcription level of NPVF was significantly increased, and the expression level of GNRH was significantly decreased in the hypothalamus with feed restriction. In addition, feed restriction significantly decreased the number of ≥2.5 mm follicles in the ovaries. In the ≥2.5 mm follicles, feed restriction significantly increased estradiol (E2) level in FF and the expression levels of steroidogenesis related genes (STAR, 3BHSD and CYP19A1) in GCs, while significantly decreased the expressions of FSHR and cell proliferation related genes (YAP1, CCND1 and PCNA) in GCs. Moreover, the activities of glucose metabolism enzymes (PFKP and G6PDH) were significantly decreased in GCs of the ≥2.5 mm follicles with feed restriction. Interestingly, as a precursor of nitric oxide, Arg supplementation can rescue the effects of feed restriction on follicular development by enhancing glucose metabolism and cell proliferation of GCs, and alleviating the abnormal E2 secretion in the ≥2.5 mm follicles, accompanied with recovering the expressions of NPVF and GNRH in the hypothalamus. These findings will be helpful for understanding the role of nutrition and Arg in sheep follicular development.

Metabolic profiles of moso bamboo in response to drought stress in a field investigation.

An increasing number of moso bamboo habitats are suffering severe drought events. The improvement in our understanding of the mechanisms of drought-resistance in moso bamboo benefits their genetic improvement and maintenance of forest sustainability. Here, we investigated the metabolic changes across the annual growth cycle of moso bamboo in the field under drought stress using liquid chromatography coupled to mass spectrometry (LC-MS) based on untargeted metabolomic profiling. Our results showed that the metabolic profiles induced by drought stress were relatively consistent among the three growth stages. Specifically, most responsive metabolites exhibited enhanced accumulation under drought stress, including anthocyanins, glycosides, organic acids, amino acids, and sugars and sugar alcohols. The potential metabolism pathways involved in the response to drought stress were mainly included into amino acid metabolism and sugar metabolism pathways. Five common responsive metabolic pathways were found among three growth stages, including linoleic acid metabolism, ubiquinone and other terpenoid-quinone biosynthesis, tyrosine metabolism, starch and sucrose metabolism and isoquinoline alkaloid biosynthesis. Overall, our findings provide new insights into the responsive mechanisms of the moso bamboo under drought stress in terms of metabolic profiles.

Effects of nitric oxide on steroidogenesis and apoptosis in goat luteinized granulosa cells.

The aim of this study was to investigate effects of nitric oxide (NO) on steroidogenesis and apoptosis in goat luteinized granulosa cells (LGCs). We cultured goat LGCs from healthy follicles in culture medium supplemented with the NO donor sodium nitroprusside (SNP) or the NO synthase inhibitor Nω-Nitro-l-arginine methyl ester hydrochloride (l-NAME), then examined steroid synthesis, oxidative stress and apoptosis in vitro. The results showed that SNP treatment significantly increased the cGMP concentration in the LGCs (P < 0.05), whereas the l-NAME treatment significantly decreased cGMP concentration (P < 0.05). Then Inhibition of NO production significantly inhibited the expression of CYP19A1, a key gene that is involved in sex steroid hormones synthesis and is responsible for the decrease of E2. Inhibition of NO production resulted in an increased percentage of apoptosis, which was accompanied by upregulating expression levels of apoptosis-related markers BAX, CASP3 and CASP9. These data indicate that NO is required for goat LGCs steroidogenesis and cell survival. Furthermore, Inhibition of NO production decreased the expression of mitochondrial biogenesis related genes and proteins (PPARGC1A, NRF-1 and TFAM) and the mtDNA copy number. Simultaneously, inhibition of NO production suppressed the transcription and translation of SOD, GPX1, and CAT, and decreased the glutathione level and increased the 8-OHdG level. However, SNP treatment increased the expression of genes involved in mitochondrial function and biogenesis, and elevated the anti-oxidant stress system and steroid synthesis. Together, our results indicate that NO may up-regulate the expression of PPARGC1A and its downstream factors through the cGMP pathway, thereby decreasing granulosa cell apoptosis, and may participate in the regulation of granulocyte steroid production through the mitochondrial-dependent pathway.

[Effect of litterfall input on soil respiration and its temperature sensitivity in moso bamboo forest under simulated drought.] / æ¨¡æ‹Ÿå¹²æ—±ä¸‹å‡‹è½ç‰©è¾“å ¥å¯¹æ¯›ç«¹æž—åœŸå£¤å‘¼å¸åŠæ¸©åº¦æ•æ„Ÿæ€§çš„å½±å“.

Increases in drought frequency and intensity under climate change will have great impacts on the carbon cycle of forest ecosystems. Understanding the responses of soil respiration and its temperature sensitivity to drought is necessary, when we assess whether soil is a carbon sink or source. The effects of litterfall input on soil respiration, temperature sensitivity and its lagging effect were studied in moso bamboo forests under simulated drought by ceiling method in the field with three litterfall treatments, i.e., ambient litterfall (unchanged, LU), litter addition (LA) and litter removal (LR). The results showed that LU decreased annual soil respiration rate in drought treatment (2.34 Μmol·m-2·s-1), compared with that in the control (3.15 Μmol·m-2·s-1) with ambient natural rainfall. LR showed stronger effect on soil respiration than LA. Compared with LU, LR decreased soil respiration rate by 21.0% in ambient condition and by 20.9% in drought treatment, while LA led to 5.3% increase only in drought treatment. Such a result indicated that the effects of LA and LR on soil respiration rate were stronger than LU in the drought condition. Drought decreased the temperature sensitivity of soil respiration by 8.4%, while LA and LR reduced that by 15.4% and 7.6%, respectively. The cumulative CO2 emissions during the whole 18 months were 7.35 and 5.40 kg CO2·m-2 in the control and drought treatment. Compared with LU, LA increased the cumulative CO2 emissions by 1.8% and 10.7%, and LR decreased that by 19.9% and 18.0% in the control and drought treatments. Our results indicated that the relationship between the litterfall amount (addition or removal) and soil respiration rate was nonlinear. The significant lagging effect may be caused by the decrease in root growth and microbial activity due to decreased soil water availability in drought treatment. Litterfall played a more important role in soil CO2 emission under drought, and thus litterfall was a crucial factor in soil carbon emission in the context of climate change.

Orbital ordering to orbital glass transition in spinel FeCr(2-x)Al(x)S4 (0 ⩽ x ⩽ 0.2).

The polycrystalline (PC) sample of FeCr2S4 displays orbital ordering around TOO ∼ 9 K, while single crystal sample shows orbital glass. In this paper, with the substitution of Al for Cr, a step by step transition from the orbital ordering to the orbital glass is reported in FeCr(2-x)Al(x)S4 (0 ⩽ x ⩽ 0.2). For PC FeCr2S4, the onset of long-range orbital order at TOO is evidenced by the appearance of a step-like transition in the temperature dependence of the magnetization (M(T)), a small kink at about 5.5 T below 9 K in the isotherms' magnetic field dependence of the magnetization (M(H)) curves as well as a λ-type anomaly in specific heat. With increasing Al content, the TOO decreases gradually. For the samples with x ⩾ 0.1, the orbital ordering is replaced by orbital glass, where the specific heat obeys a T(2)-dependence. The calculated residual orbital entropy consistently increases with x, implying the progressive freezing of the orbital moments and the coexistence of orbital ordering and orbital glass in the middle doping level.

Occupational health nursing practice, education, and research in Korea. An international update.

1. In Korea, occupational health nurses have been working as health managers at the workplace and as part of a hospital based group occupational health service since 1991. The role of occupational health manager, required by law, includes providing preventive and primary care, safety management, and inspection of the work environment. 2. Recently, occupational health nursing practice-based lecture has increased, and more emphasis has been placed on the process of occupational health nursing in both undergraduate and graduate programs. 3. The Korean Association of Occupational Health Nurses and the Korean Academic Society of Occupational Health Nursing have been working to develop professional competence for occupational health nurses since 1991. 4. Until the mid 1990s, occupational health nursing research focused primarily on role and job satisfaction of occupational health nurses. However, the number of research studies has dramatically increased and, gradually, survey studies have been replaced by studies with experimental design.