Targeted deletion of CD244 on monocytes promotes differentiation into anti-tumorigenic macrophages and potentiates PD-L1 blockade in melanoma.

BACKGROUND: In the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244. METHODS: To directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma. The phenotype and function of tumor-infiltrating macrophages along with antigen-specific CD8 T cells were analyzed by flow cytometry and single cell RNA sequencing data analysis, and the molecular mechanism underlying anti-tumorigenic macrophage differentiation, antigen presentation, phagocytosis was investigated ex vivo. Finally, the clinical feasibility of CD244-negative monocytes as a therapeutic modality in melanoma was confirmed by adoptive transfer experiments. RESULTS: CD244fl/flLysMcre mice demonstrated a significant reduction in tumor volume (61% relative to that of the CD244fl/fl control group) 14 days after tumor implantation. Within tumor mass, CD244fl/flLysMcre mice also showed higher percentages of Ly6Clow macrophages, along with elevated gp100+IFN-γ+ CD8 T cells. Flow cytometry and RNA sequencing data demonstrated that ER stress resulted in increased CD244 expression on monocytes. This, in turn, impeded the generation of anti-tumorigenic Ly6Clow macrophages, phagocytosis and MHC-I antigen presentation by suppressing autophagy pathways. Combining anti-PD-L1 antibody with CD244-/- bone marrow-derived macrophages markedly improved tumor rejection compared to the anti-PD-L1 antibody alone or in combination with wild-type macrophages. Consistent with the murine data, transcriptome analysis of human melanoma tissue single-cell RNA-sequencing dataset revealed close association between CD244 and the inhibition of macrophage maturation and function. Furthermore, the presence of CD244-negative monocytes/macrophages significantly increased patient survival in primary and metastatic tumors. CONCLUSION: Our study highlights the novel role of CD244 on monocytes/macrophages in restraining anti-tumorigenic macrophage generation and tumor antigen-specific T cell response in melanoma. Importantly, our findings suggest that CD244-deficient macrophages could potentially be used as a therapeutic agent in combination with immune checkpoint inhibitors. Furthermore, CD244 expression in monocyte-lineage cells serve as a prognostic marker in cancer patients.

Frozen Clay Minerals as a Potential Source of Bioavailable Iron and Magnetite.

Iron (Fe) is an essential micronutrient that affects biological production. Iron-containing clay minerals are an important source of bioavailable iron. However, the dissolution of iron-containing clay minerals at temperatures below the freezing point has not been investigated. Here, we demonstrate the enhanced reductive dissolution of iron from a clay mineral in ice in the presence of iodide (I-) as the electron donor. The accelerated production of dissolved iron in the frozen state was irreversible, and the freeze concentration effect was considered the main driving force. Furthermore, the formation of magnetite (Fe3O4) after the freezing process was observed using transmission electron microscopy analysis. Our results suggest a new mechanism of accelerated abiotic reduction of Fe(III) in clay minerals, which may release bioavailable iron, Fe(II), and reactive iodine species into the natural environment. We also propose a novel process for magnetite formation in ice. The freezing process can serve as a source of bioavailable iron or act as a sink, leading to the formation of magnetite.

Highly Bright Silica-Coated InP/ZnS Quantum Dot-Embedded Silica Nanoparticles as Biocompatible Nanoprobes.

Quantum dots (QDs) have outstanding optical properties such as strong fluorescence, excellent photostability, broad absorption spectra, and narrow emission bands, which make them useful for bioimaging. However, cadmium (Cd)-based QDs, which have been widely studied, have potential toxicity problems. Cd-free QDs have also been studied, but their weak photoluminescence (PL) intensity makes their practical use in bioimaging challenging. In this study, Cd-free QD nanoprobes for bioimaging were fabricated by densely embedding multiple indium phosphide/zinc sulfide (InP/ZnS) QDs onto silica templates and coating them with a silica shell. The fabricated silica-coated InP/ZnS QD-embedded silica nanoparticles (SiO2@InP QDs@SiO2 NPs) exhibited hydrophilic properties because of the surface silica shell. The quantum yield (QY), maximum emission peak wavelength, and full-width half-maximum (FWHM) of the final fabricated SiO2@InP QDs@SiO2 NPs were 6.61%, 527.01 nm, and 44.62 nm, respectively. Moreover, the brightness of the particles could be easily controlled by adjusting the amount of InP/ZnS QDs in the SiO2@InP QDs@SiO2 NPs. When SiO2@InP QDs@SiO2 NPs were administered to tumor syngeneic mice, the fluorescence signal was prominently detected in the tumor because of the preferential distribution of the SiO2@InP QDs@SiO2 NPs, demonstrating their applicability in bioimaging with NPs. Thus, SiO2@InP QDs@SiO2 NPs have the potential to successfully replace Cd-based QDs as highly bright and biocompatible fluorescent nanoprobes.

Calcipotriol, a synthetic Vitamin D analog, promotes antitumor immunity via CD4+T-dependent CTL/NK cell activation.

To overcome the hurdles of immunotherapy, we investigated whether calcipotriol, a synthetic vitamin D analog, could overcome the immune evasion of glioblastoma multiforme (GBM) by modulating immune responses and the immunosuppressive tumor microenvironment. Administration of calcipotriol considerably reduced tumor growth. Both in vivo and in vitro studies revealed that CD8+T and natural killer (NK) cell gene signatures were enriched and activated, producing high levels of IFN-γ and granzyme B. In contrast, regulatory T cells (Treg) were significantly reduced in the calcipotriol-treated group. The expression of CD127, the receptor for thymic stromal lymphopoietin (TSLP), is elevated in CD4+T cells and potentially supports T-cell priming. Depleting CD4+T cells, but not NK or CD8+T cells, completely abrogated the antitumor efficacy of calcipotriol. These data highlight that the calcipotriol/TSLP/CD4+T axis can activate CD8+T and NK cells with a concomitant reduction in the number of Tregs in GBM. Therefore, calcipotriol can be a novel therapeutic modality to overcome the immune resistance of GBM by converting immunologically "cold" tumors into "hot" tumors. DATA AVAILABILITY: Data are available upon reasonable request. The RNA-seq dataset comparing the transcriptomes of control and calcipotriol-treated GL261 tumors is available from the corresponding author upon request.

Targeting TCTP sensitizes tumor to T cell-mediated therapy by reversing immune-refractory phenotypes.

Immunotherapy has emerged as a powerful approach to cancer treatment. However, immunotherapeutic resistance limits its clinical application. Therefore, identifying immune-resistant factors, which can be targeted by clinically available drugs and it also can be a companion diagnostic marker, is needed to develop combination strategies. Here, using the transcriptome data of patients, and immune-refractory tumor models, we identify TCTP as an immune-resistance factor that correlates with clinical outcome of anti-PD-L1 therapy and confers immune-refractory phenotypes, decreased T cell trafficking to the tumor and resistance to cytotoxic T lymphocyte-mediated tumor cell killing. Mechanistically, TCTP activates the EGFR-AKT-MCL-1/CXCL10 pathway by phosphorylation-dependent interaction with Na, K ATPase. Furthermore, treatment with dihydroartenimsinin, the most effective agent impending the TCTP-mediated-refractoriness, synergizes with T cell-mediated therapy to control immune-refractory tumors. Thus, our findings suggest a role of TCTP in promoting immune-refractoriness, thereby encouraging a rationale for combination therapies to enhance the efficacy of T cell-mediated therapy.

Silver-Assembled Silica Nanoparticles in Lateral Flow Immunoassay for Visual Inspection of Prostate-Specific Antigen.

Prostate-specific antigen (PSA) is the best-known biomarker for early diagnosis of prostate cancer. For prostate cancer in particular, the threshold level of PSA <4.0 ng/mL in clinical samples is an important indicator. Quick and easy visual detection of the PSA level greatly helps in early detection and treatment of prostate cancer and reducing mortality. In this study, we developed optimized silica-coated silver-assembled silica nanoparticles (SiO2@Ag@SiO2 NPs) that were applied to a visual lateral flow immunoassay (LFIA) platform for PSA detection. During synthesis, the ratio of silica NPs to silver nitrate changed, and as the synthesized NPs exhibited distinct UV spectra and colors, most optimized SiO2@Ag@SiO2 NPs showed the potential for early prostate cancer diagnosis. The PSA detection limit of our LFIA platform was 1.1 ng/mL. By applying each SiO2@Ag@SiO2 NP to the visual LFIA platform, optimized SiO2@Ag@SiO2 NPs were selected in the test strip, and clinical samples from prostate cancer patients were successfully detected as the boundaries of non-specific binding were clearly seen and the level of PSA was <4 ng/mL, thus providing an avenue for quick prostate cancer diagnosis and early treatment.

Wikstroemiaganpi Extract Improved Atopic Dermatitis-Like Skin Lesions via Suppression of Interleukin-4 in 2,4-Dinitrochlorobenzene-Induced SKH-1 Hairless Mice.

Plants of the genus Wikstroemia are used in Chinese traditional medicine to treat inflammatory diseases, such as arthritis, bronchitis, and pneumonia. The present study was designed to determine whether Wikstroemia ganpi (Siebold and Zucc.) Maxim. offers a potential means of treating 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) in mice. Symptoms such as redness, edema, and keratinization in AD mice induced by DNCB were alleviated by the co-application of an ethanolic extract of W. ganpi for 2 weeks. The severity of skin barrier function damage was evaluated by measuring TEWL (transepidermal water loss). TEWLs of DNCB sensitized mouse dorsal skin were reduced by the application of a W. ganpi ethanolic extract, and skin hydration was increased. In addition, the infiltration of inflammatory cells into the dermis was significantly reduced, as were blood levels of IgE and IL-4, which play an important role in the expression of AD. The results of this experiment suggest that W. ganpi is a potential therapeutic agent for AD.

Au-Ag assembled on silica nanoprobes for visual semiquantitative detection of prostate-specific antigen.

BACKGROUND: Blood prostate-specific antigen (PSA) levels are widely used as diagnostic biomarkers for prostate cancer. Lateral-flow immunoassay (LFIA)-based PSA detection can overcome the limitations associated with other methods. LFIAbased PSA detection in clinical samples enables prognosis and early diagnosis owing to the use of high-performance signal reporters. RESULTS: Here, a semiquantitative LFIA platform for PSA detection in blood was developed using Au-Ag nanoparticles (NPs) assembled on silica NPs (SiO2@Au-Ag NPs) that served as signal reporters. Synthesized SiO2@Au-Ag NPs exhibited a high absorbance at a wide wavelength range (400-800 nm), with a high scattering on nitrocellulose membrane test strips. In LFIA, the color intensity of the test line on the test strip differed depending on the PSA concentration (0.30-10.00 ng/mL), and bands for the test line on the test strip could be used as a standard. When clinical samples were assessed using this LFIA, a visual test line with particular color intensity observed on the test strip enabled the early diagnosis and prognosis of patients with prostate cancer based on PSA detection. In addition, the relative standard deviation of reproducibility was 1.41%, indicating high reproducibility, and the signal reporter showed good stability for 10 days. CONCLUSION: These characteristics of the signal reporter demonstrated the reliability of the LFIA platform for PSA detection, suggesting potential applications in clinical sample analysis.

Lateral Flow Immunoassay with Quantum-Dot-Embedded Silica Nanoparticles for Prostate-Specific Antigen Detection.

Prostate cancer can be detected early by testing the presence of prostate-specific antigen (PSA) in the blood. Lateral flow immunoassay (LFIA) has been used because it is cost effective and easy to use and also has a rapid sample-to-answer process. Quantum dots (QDs) with very bright fluorescence have been previously used to improve the detection sensitivity of LFIAs. In the current study, a highly sensitive LFIA kit was devised using QD-embedded silica nanoparticles. In the present study, only a smartphone and a computer software program, ImageJ, were used, because the developed system had high sensitivity by using very bright nanoprobes. The limit of PSA detection of the developed LFIA system was 0.138 ng/mL. The area under the curve of this system was calculated as 0.852. The system did not show any false-negative result when 47 human serum samples were analyzed; it only detected PSA and did not detect alpha-fetoprotein and newborn calf serum in the samples. Additionally, fluorescence was maintained on the strip for 10 d after the test. With its high sensitivity and convenience, the devised LFIA kit can be used for the diagnosis of prostate cancer.

Comparison of Long Term Follow-up Chest CT Imaging in Adult and Pediatric Patients with Humidifier Disinfectant-related Lung Injury.

BACKGROUND: To compare the chest computed tomography (CT) images of children and adults in families with clusters of humidifier disinfectant-related lung injury (HDLI) after cessation of exposure to humidifier disinfectant (HD). METHODS: We reviewed medical records of 19 families with 43 patients (21 adults, 22 children) among families, which had at least one adult and one child with HDLI. Each family was exposed to the same HD exposure environment. RESULTS: In adults, centrilobular nodules were predominant (95.2%) in chronic HDLI findings after cessation of exposure to HD, however, in children, normal pattern was most prevalent on chest CT (45.5%), followed by centrilobular nodule (36.4%), bizarre lung cysts (36.4%), and reticulation (13.6%). CONCLUSION: Unlike the known chronic HDLI finding of adults, centrilobular nodules were only present in 36.4% of children. The frequency of bizarre lung cysts were significantly greater in children than that in adults after cessation of similar exposure to HD. Thus, bizarre lung cysts may be useful as another novel finding of chronic HDLI in children who have no history of pulmonary infection or other perinatal disorder such as hyaline membrane disease or other interstitial lung disease.

A work-relatedness assessment in epidemiological case investigation of occupational cancers: I. Principles.

It is important to identify the causal relationship between occupational exposure and the disease in the area of compensation because most cancers have long latent period. This review presents the principles that should be considered when evaluating the work-relatedness. We reviewed reports on occupational cancers published by the International Agency for Research on Cancer, American Conference of Governmental Industrial Hygienists, National Toxicology Program, Environmental Protection Agency, European Union, which are the world's most prestigious organizations. In addition, we reviewed relevant papers and books published in Korea. The process is conducted in the order of cancer diagnosis, exposure assessment for carcinogens, and work-relatedness assessment. The probability of causation is determined stochastically rather than deterministically. There is no absolute standard for accreditation criteria and results may vary according to expert opinions and in each country or organization. Revealing the causal relationship of occupational cancers is a difficult process owing to inconsistency in relevant epidemiological studies, lack of well-established biological mechanisms, loss of objective occupational historical data, and other complexity of individual cases. Causation is unclear in many cases. Nevertheless, the data should be reviewed in detail for each case suspected of work-related cancers, and an assessment should be made through valid and plausible logic and literature evidences.

A work-relatedness assessment in epidemiological case investigation of occupational cancers: II. Practice: an upper urinary tract cancer in a dyer.

An epidemiological case investigation of occupational cancer is conducted to determine the causation between the cancer and the worker's job. This review describes the overall process of work-relatedness assessment of the epidemiological case investigation through a case of upper urinary tract cancer (UUTC) in benzidine exposed worker in dyeing industry. Medical referrals, occupational history, material safety data sheet, and working environment monitoring submitted by the Korea Workers' Compensation and Welfare Service were reviewed. We further investigated literatures about the cotton dyeing industry, the domestic law and working environment monitoring reports. Benzidine was listed as an International Agency for Research on Cancer risk factor only for bladder cancer among urinary tract cancers, requiring different logical grounds for establishing causation. A literature review was conducted on the metabolic pathways of benzidine to establish biological plausibility. In addition, several papers were investigated that UUTC and bladder cancer share risk factors to extrapolate the epidemiological studies of bladder cancer. Epidemiologic studies of benzidine and bladder cancer were investigated. The worker is a 71-year-old man and performed dyeing and transporting at several dyeing factories for 29 years. The worker was diagnosed with UUTC based on radiologic and histologic results. It was critical to consider that he worked as a dyer for 3 years. The cancer was diagnosed in 2018, with a latent period of approximately 35 years. The worker performed cotton dyeing, and benzidine-based dye was mainly used. The quantitative exposure level of benzidine was reported from non-detection to 397.4 µg/m3. In biological metabolisms, N-acetylhydroxylamine changes DNA structure of urothelium. As a result of reviewing 4 epidemiological studies, the standardized incidence ratio and standardized mortality ratio were significantly high with 3 years of exposure. Work-relatedness was finally assessed as probable based on biological mechanisms and epidemiological evidence. This review will help solutions for work-relatedness assessment processes.

Characteristics of a new respiratory syndrome associated with the use of a humidifier disinfectant: humidifier disinfectant-related respiratory syndrome (HDRS).

OBJECTIVES: The purpose of this study was to characterize a new respiratory syndrome associated with exposure to a humidifier disinfectant (HD) in South Korea that is distinct from the well-known HD-related lung injury (HDLI). The authors identified this condition in 24 study subjects who were family members of patients with definite or probable HDLI (referred to as index cases), and were exposed to HD in the same room as the index cases. MATERIAL AND METHODS: The authors reviewed medical records of 236 family members in 110 families who were exposed to HD in the same rooms and residences as the index cases. RESULTS: They identified 24 family members who were exposed to HD in the same rooms and residences as the index cases, and who developed respiratory disorders that were distinct from HDLI. The clinical signs and symptoms of these individuals were in the upper respiratory tract, such as allergic rhinitis and croup, or in the lower respiratory tract, such as bronchitis and pneumonia. The diffusing capacity of the lung fordetermicarbon monoxide was reduced in 9 of 12 children (data not available for 1 child), and in 4 of 5 adults (data not available for 6 adults). The percent forced vital capacity and forced expiratory volume in one second/forced vital capacity ratios were within the normal ranges in most patients. The computed tomography findings, which mostly indicated non-specific inflammation, were inconsistent with the radiological diagnostic criteria for HDLI, but were abnormal in 8 of 11 adults, and in 2 of 13 children. CONCLUSIONS: The authors propose a new condition, i.e., HD-related respiratory syndrome (HDRS), which is characterized by mild to moderate or atypical respiratory symptoms and signs, and is related to HD exposure, but is distinct from HDLI. The recognition of HDRS may provide a basis for understanding the natural history of HD-related respiratory problems, and for capturing the whole spectrum of HD-related clinical manifestations in the respiratory tract. Int J Occup Med Environ Health. 2020;33(6):829-39.

Effects of job stress on symptoms of bipolar spectrum disorder in an electronic parts manufacturing company.

BACKGROUND: Mental illness is known to be caused by genetic, biological, and environmental risk factors. Although previous studies have established the link between mental illness and job stress, most of them are limited to major depression disorder. Therefore, this study examined the relationship between job stress and bipolar spectrum disorder (BSD). METHODS: This is a cross-sectional study based on a survey conducted in April 2017 at an electronic parts manufacturing company in Busan. In a total of 441 workers, the degree of BSD was identified using the Korean version of the Mood Disorder Questionnaire, and the degree of job stress was identified using the Korean Occupational Stress Scale Short Form. This study also identified general characteristics of workers and job-related factors. The χ2 test and Fisher's exact test was conducted to determine the differences among the variables, based on BSD. Multiple logistic regression analysis was conducted to determine the influence of independent variables on BSD. RESULTS: Cross-analysis showed significant differences between the BSD high-risk and low-risk groups regarding age, sex, occupation, smoking, problem drinking, job stress total score, occupational climate, and major depression disorder symptom. In addition, the significant differences between the BSD high-risk and low-risk groups about job stress were observed in terms of job demand, job insecurity, and occupational climate. A multiple logistic regression analysis revealed that the high-risk group in the job stress group had a higher effect on BSD than the low-risk group (odds ratio [OR]: 2.32, 95% confidence interval [CI]: 1.10-4.88). Among the categories of job stress, high-risk groups in 3 areas-job demand (OR: 2.56, 95% CI: 1.27-5.17), job insecurity (OR: 4.42, 95% CI: 1.19-16.42), and occupational climate (OR: 2.55, 95% CI: 1.29-5.05)-were more likely to have an impact on BSD than the low-risk groups. CONCLUSIONS: This study demonstrated that the high-risk groups of job stress total score, job demand, job insecurity, and occupational climate had a more significant effect on BSD than the low-risk groups. As workers with BSD may have difficulties in their work and personal lives, there is a need to manage job stress to prevention of BSD.

NK Cell-Based Immunotherapies in Cancer.

With the development of technologies that can transform immune cells into therapeutic modalities, immunotherapy has remarkably changed the current paradigm of cancer treatment in recent years. NK cells are components of the innate immune system that act as key regulators and exhibit a potent tumor cytolytic function. Unlike T cells, NK cells exhibit tumor cytotoxicity by recognizing non-self, without deliberate immunization or activation. Currently, researchers have developed various approaches to improve the number and anti-tumor function of NK cells. These approaches include the use of cytokines and Abs to stimulate the efficacy of NK cell function, adoptive transfer of autologous or allogeneic ex vivo expanded NK cells, establishment of homogeneous NK cell lines using the NK cells of patients with cancer or healthy donors, derivation of NK cells from induced pluripotent stem cells (iPSCs), and modification of NK cells with cutting-edge genetic engineering technologies to generate chimeric Ag receptor (CAR)-NK cells. Such NK cell-based immunotherapies are currently reported as being promising anti-tumor strategies that have shown enhanced functional specificity in several clinical trials investigating malignant tumors. Here, we summarize the recent advances in NK cell-based cancer immunotherapies that have focused on providing improved function through the use of the latest genetic engineering technologies. We also discuss the different types of NK cells developed for cancer immunotherapy and present the clinical trials being conducted to test their safety and efficacy.

Simultaneous and Synergic Production of Bioavailable Iron and Reactive Iodine Species in Ice.

The bioavailable iron is essential for all living organisms, and the dissolution of iron oxide contained in dust and soil is one of the major sources of bioavailable iron in nature. Iodine in the polar atmosphere is related to ozone depletion, mercury oxidation, and cloud condensation nuclei formation. Here we show that the chemical reaction between iron oxides and iodide (I-) is markedly accelerated to produce bioavailable iron (Fe(II)aq) and tri-iodide (I3-: evaporable in the form of I2) in frozen solution (both with and without light irradiation), while it is negligible in aqueous phase. The freeze-enhanced production of Fe(II)aq and tri-iodide is ascribed to the freeze concentration of iron oxides, iodides, and protons in the ice grain boundaries. The outdoor experiments carried out in midlatitude during a winter day (Pohang, Korea: 36°0' N, 129°19' E) and in an Antarctic environment (King George Island: 62°13' S 58°47' W) also showed the enhanced generation of Fe(II)aq and tri-iodide in ice. This study proposes a previously unknown abiotic mechanism and source of bioavailable iron and active iodine species in the polar environment. The pulse input of bioavailable iron and reactive iodine when ice melts may influence the oceanic primary production and CCN formation.

Defective Localization With Impaired Tumor Cytotoxicity Contributes to the Immune Escape of NK Cells in Pancreatic Cancer Patients.

Tumor-infiltrating lymphocytes (TILs), found in patients with advanced pancreatic ductal adenocarcinoma (PDAC), are shown to correlate with overall survival (OS) rate. Although majority of TILs consist of CD8+/CD4+ T cells, the presence of NK cells and their role in the pathogenesis of PDAC remains elusive. We performed comprehensive analyses of TIL, PBMC, and autologous tumor cells from 80 enrolled resectable PDAC patients to comprehend the NK cell defects within PDAC. Extremely low frequencies of NK cells (<0.5%) were found within PDAC tumors, which was attributable not to the low expression of tumor chemokines, but to the lack of chemokine receptor, CXCR2. Forced expression of CXCR2 in patients' NK cells rendered them capable of trafficking into PDAC. Furthermore, NK cells exhibited impaired cell-mediated killing of autologous PDAC cells, primarily due to insufficient ligation of NKG2D and DNAM-1, and failed to proliferate within the hypoxic tumor microenvironment. Importantly, these defects could be overcome by ex-vivo stimulation of NK cells from such patients. Importantly, when the proliferative capacity of NK cells in vitro was used to stratify patients on the basis of cell expansion, patients whose NK cells proliferated <250-fold experienced significantly lower DFS and OS than those with ≥250-fold. Ex-vivo activation of NK cells restored tumor trafficking and reactivity, hence provided a therapeutic modality while their fold expansion could be a potentially significant prognostic indicator of OS and DFS in such patients.

Synthesis and Electroresponse Activity of Porous Polypyrrole/Silica-Titania Core/Shell Nanoparticles.

Inverted conducting polymer/metal oxide core/shell structured pPPy/SiO2-TiO2 nanoparticles were prepared as electrorheological (ER) materials using sequential experimental methods. The core was synthesized via the low-temperature self-assembly of PPy and SiO2 materials, and the outer TiO2 shell was easily coated onto the core part using a sol-gel method and a titanium isopropoxide precursor. Sonication-mediated etching and redeposition were employed to etch out SiO2 portions from the core part to blend with TiO2 shells. Each step in nanoparticle synthesis involved morphological and physical changes to the surface area and porosity, with subsequent changes in the intrinsic properties of the materials. Specifically, the electrical conductivity and dielectric properties were successfully altered. The final pPPy/SiO2-TiO2 nanoparticle configuration was optimized for ER applications, offering low electrical conductivity, high dielectric properties, and increased dispersion stability. pPPy/SiO2-TiO2 nanoparticles exhibited 24.7- and 2.7-fold enhancements in ER performance compared to that of PPy-SiO2 and PPy-SiO2/TiO2 precursor nanoparticles, respectively. The versatile method proposed in this study for the synthesis of inverted conducting polymer/metal oxide core/shell nanoparticles shows great potential for the development of custom-designed ER materials.

Ovarian cancer in a former asbestos textile factory worker: a case report.

BACKGROUND: The International Agency for Research on Cancer (IARC) defined that asbestos is a group 1 substance that causes lung cancer, mesothelioma (pleura and peritoneum), laryngeal cancer, and ovarian cancer in humans. Many studies on lung cancer, and mesothelioma caused by asbestos exposure have been conducted, but there was no case report of ovarian cancer due to asbestos exposure in Korea. We describe a case of ovarian cancer caused by asbestos exposure in a worker who worked at an asbestos textile factory for 3 years and 7 months in the late 1970s. CASE PRESENTATION: A 57-year-old woman visited the hospital because she had difficulty urinating. Ovarian cancer was suspected in radiologic examination, and exploratory laparotomy was performed. She was diagnosed with epithelial ovarian cancer. The patient did not undergo postoperative chemotherapy and recovered. She joined the asbestos factory in March 1976 and engaged in asbestos textile twisting and spinning for 1 year, 2 years and 7 months respectively. In addition, she lived near the asbestos factory for more than 20 years. There was no other specificity or family history. CONCLUSION: Considering the patient's occupational and environmental history, it is estimated that she had been exposed to asbestos significantly, so we determined that ovarian cancer in the patient is highly correlated with the occupational exposure of asbestos and environmental exposure is a possible cause as well. Social devices are needed to prevent further exposure to asbestos. It is also necessary to recognize that ovarian cancer can occur in workers who have previously been exposed to asbestos, and the education and social compensation for those workers are needed.

Review of carcinogenicity of hexavalent chrome and proposal of revising approval standards for an occupational cancers in Korea.

BACKGROUND: The objective of this study is to suggest revised recognition standards for occupational disease due to chromium (VI) by reflecting recent domestic and international research works and considering domestic exposure status with respect to target organs, exposure period, and cumulative exposure dose in relation to the chromium (VI)-induced occupational disease compensation. METHODS: In this study, the reports published by major international institutions such as World Health Organization (WHO) International Agency for Research on Cancer (IARC) (2012), Occupational Safety and Health Administration (OSHA) (2006), National Institute for Occupational Safety and Health (NIOSH) (2013), American Conference of Governmental Industrial Hygienists (ACGIH) (2004), National Toxicology Program (NTP) (2014), and Agency for Toxic Substances and Disease Registry (ASTDR) (2012) were reviewed and the recent research works searched by PubMed were summarized. RESULTS: Considering the recent research works and the domestic situation, only lung cancer is conserved in the legislative bill in relation to chromium (VI), and the exposure period is not included in the bill. Nasal and paranasal sinus cancer was excluded from the list of cancers that are compensated as the chromium (VI)- induced occupational disease, while lung cancer remains in the list. In the view of legislative unity, considering the fact that only the cancers having sufficient evidence are included in the conventional list of cancers compensated as occupational disease, nasal and paranasal sinus cancer having limited evidence were excluded from the list.The exposure period was also removed from the legislative bill due to the insufficient evidence. Recent advices in connection with cumulative exposure dose were proposed, and other considerable points were provided with respect to individual occupational relevance. CONCLUSIONS: It is suggested that the current recognition standard which is "Lung cancer or nasal and paranasal sinus cancer caused by exposure to chromium (VI) or compounds thereof (exposure for two years or longer), or nickel compounds" should be changed to "Lung cancer caused by exposure to chromium (VI) or compounds thereof, and lung cancer or nasal and paranasal sinus cancer caused by exposure to nickel compounds".