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Understanding the function of the nasal vasculature in homeostasis and pathogenesis of common nasal diseases is important. Here we describe an extensive network of venous sinusoids (VSs) in mouse and human nasal mucosa. The endothelium of the VSs expressed Prox1 (considered to be a constitutive marker of lymphatic endothelium) and high levels of VCAM-1 and exhibited unusual cell-to-cell junctions. VSs are supported by circular smooth muscle cells (SMCs) and surrounded by immune cells. The nasal mucosa also showed a rich supply of lymphatic vessels with distinctive features, such as the absence of the lymphatic marker LYVE1 and sharp-ended capillaries. In mouse models of allergic rhinitis or acute Coronavirus Disease 2019 (COVID-19) infection, Prox1+ VSs were regressed or compromised. However, in aged mice, the VSs lost the SMC support and were expanded and enlarged. Our findings demonstrate three-dimensional morphological and molecular heterogeneities of the nasal vasculature and offer insights into their associations with nasal inflammation, infection and aging.

Objectives. Obesity, which induces chronic low-grade systemic inflammation in the human body, is a known risk factor for various diseases. Recent studies have shown associations between various otorhinolaryngological diseases and obesity. In particular, inflammatory sinonasal diseases have been found to be strongly associated with obesity-related proinflammatory mediators. Many studies have been conducted to identify therapeutic agents for controlling obesity-related inflammatory airway diseases. Ghrelin, an endogenous peptide from the stomach, has anti-inflammatory and antioxidative effects in a wide range of tissues. However, the effect of ghrelin on the regulation of mucus secretion has not yet been studied in the human nasal mucosa. Therefore, we investigated the effects of ghrelin on lipopolysaccharide (LPS)/leptin-mediated MUC5AC expression and mechanisms involved in human nasal epithelial cells (HNEpCs).Methods. In HNEpCs, the effect and signaling pathways of ghrelin on LPS/leptin-induced MUC5AC expression were examined using reverse transcription polymerase chain reaction, real-time polymerase chain reaction, enzyme immunoassays, Western blotting, and immunofluorescence staining.Results. Growth hormone secretagogue receptor 1a (GHSR1a) was expressed in the HNEpCs. Ghrelin downregulated LPS/leptin-induced MUC5AC expression, which was abolished by D-Lys-3-growth hormone-releasing peptide 6 (D-Lys-3-GHRP-6). Ghrelin significantly inhibited LPS/leptin-activated extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs). These ghrelin-mediated changes in MAPK activation were abolished by D-Lys-3-GHRP-6. These results showed that ghrelin inhibits LPS/leptin-induced MUC5AC overexpression by modulating the ERK1/2 and p38 MAPK pathways in HNEpCs.Conclusion. These findings suggest that ghrelin is a potential therapeutic agent for treating obesity-related inflammatory sinonasal diseases.

Cinnamon water extract was found to slow the colonic transit time of stools and to alter the gut microbiota composition and its metabolites, thereby, alleviating diarrhea symptoms. Metabolic pathways related to gut microbiota were predicted.

Empty nose syndrome is a rare complication caused by excessive removal of normal tissues after nose surgery. The main symptoms of empty nose syndrome are paradoxical nasal obstruction, dryness, crust and dyspnea. Medical treatments such as irrigation, humidification, and ointment are not very effective, so surgical treatments to reconstruct the normal nasal cavity using implant materials are often considered. If the implant is not properly inserted, the symptoms persist and the implant must be removed again, resulting in the only donor site complications. Therefore, it is essential to treat the implant well and insert it precisely. Here we describe a surgical procedure to manage implant materials using autologous costal cartilage in the form of block, diced, and crushed cartilage for augmentation technique.

Diesel exhaust particle (DEP) is a harmful kind of particulate matter known to exacerbate pre-existing respiratory diseases. Although their adverse effects on airway pathologies have been widely studied, the mechanistic analysis of signaling pathways and potential targets in reducing DEP-induced mucin secretion and pro-inflammatory cytokine production remain elusive. We, for the first time, investigated the effects of Korean Red Ginseng (KRG) extracts on mucin overproduction and airway inflammation induced by DEP.The effects of KRG and saponin on DEP-induced expression of MUC5AC and interleukin (IL)-6/8 were examined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) in human airway epithelial NCI-H292 cells. We conducted Western blotting analysis to analyze the associated signaling pathways. To evaluate the effects of saponin treatment on DEP-induced MUC5AC expression and inflammatory cell infiltrations in ovalbumin (OVA)-sensitized mice, immunohistochemical (IHC) staining and real-time PCR were implemented.The KRG extracts markedly attenuated DEP-induced MUC5AC expression in vitro by inhibiting the TLR4/TRIF/NF-κB pathway. Furthermore, KRG and saponin inhibited DEP-induced pro-inflammatory cytokine IL-6/8 production. The in vivo study revealed that saponin blocked DEP-induced inflammation, mucin production and MUC5AC expression.Our study revealed that KRG extracts have inhibitory effects on DEP-induced expression of MUC5AC and the production of pro-inflammatory cytokines. This finding provides novel insights into the mechanism by which saponin alleviates diesel-susceptible airway inflammation, elucidating its potential as a phytotherapeutic agent for inflammatory pathologies of airway.

Purpose: To report a case of orbital apex syndrome and central retinal vein occlusion after blow-out fracture repair.Case summary: A 22-year-old man who underwent emergency re-operation in a department of plastic surgery due to pain, decreased visual acuity, and ophthalmoplegia in all direction after orbital blow-out fracture repair was referred to ophthalmologist on postoperative day 2 and there was no improvement in symptoms. He showed severe complications, including optic neuropathy and ophthalmoplegia in all direction, central retinal vein occlusion, and outer retinal disruption caused by orbital apex hemorrhage. Although we were concerned that it was too late, we started high dose steroid intravenous pulse treatment and the visual acuity, ophthalmoplegia, and retinal findings were improved. However, the optic atrophy and visual field defect did not.Conclusions: After a complicated blow-out fracture repair in other department, if a patient shows severely decreased visual acuity or ocular movement limitation, a thorough and immediate ophthalmologic examination is recommended. During ophthalmologic examination, meticulous examination of the entire eye, including the retina, is required, in addition to general orbital complications. A relatively good prognosis can be expected through accurate cause analysis and appropriate treatment for the confirmed abnormal findings.

Background. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a novel infectious respiratory disease called COVID-19, which is threatening public health worldwide. SARS-CoV-2 spike proteins connect to the angiotensin converting enzyme 2 (ACE2) receptor through the receptor binding domain and are then activated by the transmembrane protease serine subtype 2 (TMPRSS2). The ACE2 receptor is highly expressed in human nasal epithelial cells. Nasal ciliated cells are primary targets for SARS-CoV-2 replication. However, the effect of SARS-CoV-2 on the upper respiratory tract remains unknown, thus leading to the purpose of our study. We investigate the effects of SARS-CoV-2 on cytokines and mucin expression in human nasal epithelial cells. Methods. We investigated the effects of the SARS-CoV-2 spike protein receptor binding domain (RBD) on cytokines (IL-1β, IL-6, and IL-8) and MUC5AC/5B expression via real-time PCR, ELISA, periodic acid-Schiff (PAS) staining, and immunofluorescence staining in cultured human nasal epithelial cells. Results. The mRNA expression and protein production of cytokines (IL-1β, IL-6, and IL-8) and MUC5AC/5B were increased by SARS-CoV-2 spike protein RBD. ACE2 receptor inhibitor suppressed the expression of cytokines (IL-1β, IL-6, and IL-8) and MUC5AC/5B induced by SARS-CoV-2 spike protein RBD. Conclusions. SARS-CoV-2 induced cytokines (IL-1β, IL-6, and IL-8) and MUC5AC/5B expression through the ACE 2 receptor in human nasal epithelial cells. Therefore, ACE2 receptor inhibitors can be an effective therapeutic option for SARS-CoV-2 infection.

Purpose: We sought correlations between the subfoveal choroidal thickness (SCT) and changes in the levels of aqueous humor cytokines before and after anti‐vascular endothelial growth factor (anti‐VEGF) treatment of patients with neovascular age‐related macular degeneration (nAMD) and pachychoroid neovasculopathy.Methods: We measured changes in the SCT and levels of aqueous humor cytokines (VEGF, soluble VEGF receptor‐2 [sVEGFR‐ 2], platelet‐derived growth factor [PDGF]‐AA, monocyte chemoattractant protein 1 [MCP‐1], interleukin [IL]‐6, and IL‐8) after anti‐ VEGF treatment of 11 eyes of 11 nAMD patients and nine eyes of nine pachychoroid neovasculopathy patients. The aqueous humor cytokine levels were compared between the two groups.Results: After anti‐VEGF treatment, the aqueous levels of VEGF and PDGF‐AA decreased significantly, whereas that of sVEGFR‐2 increased. The amount of change in sVEGFR‐2 concentration before and after anti‐VEGF treatment correlated with the SCT and its change after treatment. nAMD patients with relatively thin SCTs and smaller SCT changes after anti‐VEGF treatment showed greater increases in sVEGFR‐2 levels following treatment. We found significant correlations among the MCP‐1, IL‐6, and IL‐8 levels in the nAMD group, and between the sVEGFR‐2 and MCP‐1, and MCP‐1 and PDGF‐AA, levels in the pachychoroid neovasculopathy group.Conclusions: Patients with nAMD exhibited significant increases in aqueous sVEGFR‐2 levels following anti‐VEGF treatment and significant correlations among the levels of the inflammatory cytokines MCP‐1, IL‐6, and IL‐8, suggesting that angiogenic factors and inflammatory cytokines may affect the pathophysiologies of the two diseases differently.

A majority (70%) of Q fever patients in South Korea do not have a history of animal contact. Therefore, unconscious environmental exposure is suspected. The aim of this study was to investigate exposure of Q fever patients to environmental contamination and animal shedding.Two goat farmers were enrolled. One was diagnosed with Q fever 3 years ago (Farm 1). Among 20 goats on Farm 1, five were tested randomly and found to be Q fever PCR-positive. Three of the five were Q fever ELISA-positive. Two of five environmental samples taken in 2015 were PCR-positive. In 2018, 17 of 18 environmental samples were PCR-positive. On Farm 2, 54 of the 77 goats were PCR-positive, and 63 were ELISA-positive. Twelve of 14 environmental samples were PCR-positive. Repeat administration of oxytetracycline to goats led to a gradual reduction in PCR-positive tests over a 5-month period. However, PCR-positivity of the farm environment persisted for 5 months.The environment on farms owned by Q fever patients was contaminated extensively and persistently, even after antibiotic treatment of goats and environmental decontamination. Undetected environmental contamination can be a major source of sporadic Q fever infection in South Korea.

BACKGROUND Diced cartilage glue (DG) grafts have been widely used in dorsal augmentation but can induce dorsal irregularities. The authors evaluated the postoperative feasibility of a crushed septal cartilage-covered diced cartilage glue (CCDG) graft. METHODS The medical records of 38 patients who underwent dorsal augmentation rhinoplasty with an open approach were retrospectively reviewed. DG graft was used in 18 patients (47.4%), and CCDG graft was used in 20 patients (52.6%). Surgical outcomes were assessed by comparing anthropometric data on facial photographs and satisfaction questionnaires on aesthetic outcomes and palpable irregularities on nasal dorsum before and after surgery. RESULTS Both groups showed successful aesthetic outcomes. Dorsal height, radix height, and tip projection were all increased postoperatively in both groups. Tip rotation did not significantly increase (p > 0.05). Both groups showed similar outcomes in terms of aesthetic satisfaction but a significant difference in palpable irregularity. CCDG graft group showed significantly better (p = 0.04) satisfaction with dorsal irregularities (4.15 ± 0.75) than the DG graft group (3.56 ± 0.92). CCDG graft group also showed significantly better mean values (p = 0.048) in the degree of irregularity by two surgeons (3.85 ± 0.65) than the DG graft group (3.25 ± 0.97). No patient had significant complaints about irregular dorsum, and none of them underwent a revision rhinoplasty. CONCLUSION CCDG graft can be a complementary option for avoiding postoperative irregular dorsum complications. LEVEL OF EVIDENCE IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Exposure to diesel exhaust particles (DEPs) and urban particles (UPs) increases the incidence of degenerative brain diseases as well as respiratory diseases. However, there is limited evidence on the mechanism of neurotoxicity on exposure to these particles. In the present study, the damage to blood–brain barrier (BBB) function by DEP or UP exposure was evaluated in bEnd.3 cells, which are derived from the brain tissue of Balb/c mice. It was demonstrated that DEP and UP exposure may induce oxidative stress via increasing reactive oxygen species (ROS) and decreasing total antioxidant capacity (TAC) level in bEnd.3 cells. In addition, cells exposed to DEP and UP demonstrated a resistance value of about 50% each compared to the value noted prior to exposure; additionally, Claudin-5 and ZO-1 expression levels were significantly decreased compared to the corresponding levels in the control. It was inferred that DEP or UP exposure diminishes the expression of tight junction proteins in endothelial cells through ROS generation, thereby enhancing endothelial membrane permeability. This study showed that DEPs or UPs induced cell permeability and oxidative stress by increasing ROS generation in bEnd.3 cells. This suggests the possibility that exposure to DEPs or UPs may compromise the integrity of the BBB and induce adverse effects in the CNS.

Objective: To evaluate the clinical efficacy and safety of cefetamet pivoxil for the treatment of acute bacterial rhinosinusitis in Korean patients compared to treatment with cefdinir. Methods: A prospective, multicenter, randomized double-blind, comparative study was conducted by the Departments of Otorhinolaryngology–Head and Neck Surgery at 17 hospitals or universities in the Republic of Korea from March 2017 to April 2019. A total of 309 patients were screened and 249 patients participated in the study. Results: Treatment with cefetamet pivoxil for 2 weeks showed 82.4% clinical cure and improvement rates in patients with acute bacterial rhinosinusitis compared to 84.68% in those taking cefdinir for 2 weeks, showing that cefetamet pivoxil administered twice a day for 2 weeks was as effective as cefdinir 3 times a day for 2 weeks for the treatment of acute bacterial rhinosinusitis. The overall adverse reaction rates of both drugs were 10.56% in the cefetamet pivoxil group and 15.49% in the cefdinir group, without serious adverse events or drug reactions. Conclusions: Cefetamet pivoxil twice a day was as efficacious and safe as cefdinir 3 times a day for the treatment of acute bacterial rhinosinusitis, which suggested that cefetamet pivoxil may be a suitable alternative to cefdinir.

Objectives. The emergence of electronic cigarettes (e-cigarettes) has created new perceptions of the tobacco market. Unlike traditional tobacco, the greatest advantage of e-cigarettes is that they have less smell and are convenient and inexpensive. Most e-cigarette smokers believe that e-cigarette smoking is less harmful than traditional smoking. Information on the effects of e-cigarettes on human health is limited, and the issue remains controversial.Methods. We studied the effects of e-cigarette vapor on mucin (MUC5AC and MUC5B) and the change of MUC5AC and MUC5B from e-cigarette liquid with or without nicotine in respiratory epithelial cells. The effects of e-cigarette vapor with or without nicotine on mucin, along with the involved signaling pathways, were investigated using reverse transcriptase-polymerase chain reaction (PCR), real-time PCR, enzyme immunoassays, and immunoblot analysis with several specific inhibitors and small interfering RNA.Results. E-cigarette vapor with or without nicotine stimulated MUC5AC, but not MUC5B, expression in respiratory epithelial cells. In addition, we showed that e-cigarette vapor with and without nicotine induced MUC5AC expression via activation of the mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase [ERK] 1/2 and p38) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways in human airway epithelial cells.Conclusion. E-cigarette vapor with and with nicotine significantly increased MUC5AC expression in human airway epithelial cells.

To compare the standardized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence of high epicenter region with non-epicenter region, serological studies were performed with a total of 3,268 sera from Daegu City and 3,981 sera from Chungbuk Province. Indirect immunofluorescence assay (IFA) for SARS-CoV-2 IgG results showed a high seroprevalence rate in the Daegu City (epicenter) compared with a non-epicenter area (Chungbuk Province) (1.27% vs. 0.91%, P = 0.0358). It is noteworthy that the highest seroprevalence in Daegu City was found in elderly patients (70’s) whereas young adult patients (20’s) in Chungbuk Province showed the highest seroprevalence. Neutralizing antibody (NAb) titers were found in three samples from Daegu City (3/3, 268, 0.09%) while none of the samples from Chungbuk Province were NAb positive. These results demonstrated that even following the large outbreak, the seropositive rate of SARS-CoV-2 in the general population remained low in South Korea.

Background and Objectives Ginsenoside Rb1 is the main metabolite of Panax ginseng. It is known to have many beneficial properties including anti-inflammatory, antitumoral and antioxidant effects. However, the therapeutic effects of ginenoside Rb1 on inflammatory airway diseases have not been elucidated. Therefore, we investigated the effects of ginsenoside Rb1 on the TGF-β1-induced mucin gene expression and epithelial-mesenchymal transition (EMT) in human airway epithelial cells.Materials and Method We evaluated the effects of ginsenoside Rb1 on the changes of MUC4, MUC5AC, occludin, claudin 4, claudin 18, neural (N)-cadherin, and epithelial (E)-cadherin expression by TGF-β1 in NCI-H292 cells using reverse, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and western blot.Results TGF-β1 significantly increased MUC4/5AC expression. Rb1 inhibited TGF-β1- induced MUC4/5AC expression. In addition, TGF-β1 significantly attenuated occludin, claudin 18, and E-cadherin expressions but induced claudin 4 and N-cadherin expressions. On the other hand, Rb1 reversed changes in the TGF-β1- mediated expressions of cell junction molecules.Conclusion These results suggest that ginsenoside Rb1 attenuates TGF-β1-induced MUC4/5AC expressions and EMT in the human airway epithelial cells. These findings are important data demonstrating the potential of ginsenoside Rb1 as a therapeutic agent for inflammatory airway diseases.

1-Nitropyrene (1-NP) is a major nitro-polycyclic aromatic hydrocarbon (nitro-PAH), and a common constituent in diesel exhaust particles (DEPs). Absorbed 1-nitropyrene is partly metabolized to 1-aminopyrene and excreted in urine. Recently, the number of diesel cars has been increasing, which could be a major cause of air pollution, resulting elevated levels of traffic-related DEPs around cities. The aim of this study was to investigate the usability of 1-aminopyrene (1-AP) as a biomarker for DEP exposure by examining the association between urinary 1-AP concentration and the amount of exposure to atmospheric 1-NP. The study subjects included 65 individuals who work on vehicular roads or bus terminals. Their 24 h urine samples were collected, and atmospheric air was sampled using a personal air sampler for 24 h. Urinary 1-AP and atmospheric nitro-PAH levels were measured using a high-pressure liquid chromatography-fluorescence detector (HPLC-FD). The average urine 1-AP concentration was 0.334 pg/g creatinine. Urinary 1-AP levels were significantly correlated with 1-NP level exposure (r = 0.385, p = 0.002) but not with the other nitro-PAHs. When the subjects were classified into high-and low-exposure groups, a significant association was only found in the high exposure group (r = 0.357, p = 0.045). In conclusion, there was a significant correlation between 1-NP exposure and urinary 1-AP concentration; therefore, urinary 1-AP level could be used as an exposure biomarker for DEP. Supplementary Information The online version contains supplementary material available at 10.1007/s43188-021-00096-z.

MUC4 is a predominant membrane-tethered mucin lubricating and protecting the epithelial surface and playing various biological roles in the renewal and differentiation of epithelial cells, cell signaling, cell adhesion, and carcinogenesis. Interestingly, recent studies have demonstrated that MUC4 expression regulates the epithelial-mesenchymal transition (EMT) of cancer cells in ovarian, pancreatic, and lung cancer. However, the effects of MUC4 expression on EMT in human airway epithelial cells are not yet well known. Here, we describe the effects of transforming growth factor beta 1 (TGF-β1)-induced MUC4 expression on EMT and evaluate its downstream signaling pathway in human airway epithelial cells. In human airway epithelial NCI-H292 cells, exposure to TGF-β1 induced expression of MUC4, CDH2, VIM and SNAI1 genes and encoded by them proteins, MUC4, N-cadherin, vimentin and Snail, and reduced the level of CDH1 and its product, E-cadherin. In MUC4-knockdown cells, TGF-β1-induced expression levels of MUC4, CDH2, VIM and SNAI1 and corresponding proteins were suppressed, but CDH1 and E-cadherin levels were not. In addition, TGF-β1-induced phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2) was suppressed, but that of Smad2/3, Akt, and p38 was not. The results of this study suggest that MUC4 silencing inhibits TGF-β1 -induced EMT via the ERK1/2 pathway, and a possible role of MUC4 in the induction of EMT in human airway epithelial cells.

There are several reports in the literature on the association between non-arteritic retinal artery occlusion (NA-RAO) and acute ischemic stroke. We investigated the burden of small vessel disease (SVD) and cerebral coincident infarction observed on cerebral magnetic resonance imaging (MRI) in patients with newly diagnosed NA-RAO. In this retrospective, observational, case-series study, consecutive patients with NA-RAO who underwent cerebral MRI within one month of diagnosis between September 2003 and October 2018 were included. The classification of NA-RAO was based on ophthalmologic and systemic examinations. We also investigated the co-incident infarction and burden of underlying SVD, which were categorized as white matter hyperintensity lesion (WMH), cerebral microbleeds (CMB), and silent lacunar infarction (SLI). Among the 272 patients enrolled in the study, 18% presented co-incident infarction and 73% had SVD, which included WMH (70%), CMB (14%), and SLI (30%). Co-incident infarction, WMH, and SLI significantly increased with age: co-incident infarction was observed in 8% of young (P = 0.002) and co-incident infarction (30%: 19%: 8%; P = 0.009). Therefore, high co-incidence of acute cerebral infarction and underlying SVD burden warrant careful neurologic examination and appropriate brain imaging, followed by management of NA-RAO. Urgent brain imaging is particularly pertinent in elderly patients with NA-RAO.

As a core component of 2D ultrasound transducers, honeycomb-shaped 1–3 connectivity piezoelectric micropillar arrays have attracted enormous attention due to their unique performance and functionality. In this paper, honeycomb-shaped 1–3 connectivity piezoelectric micropillar arrays with a high aspect-ratio were designed and fabricated by means of deep X-ray lithography and powder injection molding in six steps: preparation of lost mold, powder-binder mixing, injection molding and demolding, removal of binders, and densification of powder. A polymer-based lost mold insert was generated by a synchrotron X-ray exposure and development process. The optimal volumetric ratio between the piezoelectric powder and binders was determined by torque rheology behavior, then they were homogeneously mixed with a twin extruder mixer. To fully fill in the micro-cavities of the lost mold, rheological properties of the mixture were analyzed with a capillary rheometer using different shear rates (50–5000 s−1) and temperatures (140 °C, 150 °C, and 160 °C). After the mixture was completely injected, the lost mold was chemically dissolved in acetone and rinsed in methanol without bending or clustering of the micropillar arrays during evaporation. The binders in the injection molded portion were thermally decomposed using a continuous heating schedule of 200 °C, 390 °C, and 600 °C in argon gas under atmospheric conditions. Finally, the particles in the sample were densified into a coherent, solid mass by eliminating pores at 1300 °C. Based on the proposed micro-manufacturing process, defect-free honeycomb-shaped 1–3 connectivity piezoelectric micropillar arrays with a pattern dimension of 42 μm and aspect-ratio of 5 were successfully produced.

Background and Objectives Nicotine is oxidized into tobacco-specific nitrosamines (TSNAs; NAB, NAT, NNN, NNAL, NNK) at high temperature and high pressure. TSNAs are associated with airway diseases characterized by mucus hypersecretion as a major pathophysiologic phenomenon. The aim of study is to investigate the effect of TSNAs on mucin overexpression and its molecular mechanism in human airway epithelial cells. Materials and Method The cytotoxicity of TSNAs was evaluated using EX-Cytox and inverted microscopy. The mRNA and protein levels of MUC5AC and MUC5B were measured using real-time PCR and ELISA. Results NAB, NNN, NNAL, and NNK did not affect cell viability. NAT did not affect cell viability up to a concentration of 100 μM in human airway epithelial cells. NAT, NNN, NNAL, and NNK significantly induced MUC5AC expression, but not MUC5B expression. NAB did not affect the expression of MUC5AC and MUC5B. Propranolol (a β-adrenergic receptor antagonist) inhibited NAT, NNN, NNAL, and NNK-induced MUC5AC expression, whereas α-bungarotoxin (an α7-nicotinic acetylcholine receptor antagonist) only inhibited NNN- and NNK-induced MUC5AC expression. Conclusion These results suggested that NAT, NNN, NNAL, and NNK induce MUC5AC expression through β-adrenergic receptor and/or α7-nicotinic acetylcholine receptor in human airway epithelial cells, which may be involved in mucus hypersecretion in inflammatory airway diseases.

While the seroprevalence of SARS-CoV-2 in healthy people does not differ significantly among age groups, those aged 65 years or older exhibit strikingly higher COVID-19 mortality compared to younger individuals. To further understand differing COVID-19 manifestations in patients of different ages, three age groups of ferrets are infected with SARS-CoV-2. Although SARS-CoV-2 is isolated from all ferrets regardless of age, aged ferrets (≥3 years old) show higher viral loads, longer nasal virus shedding, and more severe lung inflammatory cell infiltration, and clinical symptoms compared to juvenile (≤6 months) and young adult (1–2 years) groups. Furthermore, direct contact ferrets co-housed with the virus-infected aged group shed more virus than direct-contact ferrets co-housed with virus-infected juvenile or young adult ferrets. Transcriptome analysis of aged ferret lungs reveals strong enrichment of gene sets related to type I interferon, activated T cells, and M1 macrophage responses, mimicking the gene expression profile of severe COVID-19 patients. Thus, SARS-CoV-2-infected aged ferrets highly recapitulate COVID-19 patients with severe symptoms and are useful for understanding age-associated infection, transmission, and pathogenesis of SARS-CoV-2., Here, Kim et al. characterize SARS-CoV-2 infection in juvenile, young, and old aged ferrets to provide a further understanding of differences in COVID-19 severity in humans at different ages. Aged ferrets have higher viral loads, shed virus longer, and mimic the transcriptomic profile of severely infected patients.

Nitropyrene (1-NP) is a specific indicator of exposure to diesel exhaust and is partly metabolized to 1-aminopyrene (1-AP) and

Three industrial waste incinerators (IWIs) were built in 1999, 2001, and 2010, within a 3 km radius of a town with a population of around 5000 in Korea. This study evaluated whether residents near these three IWIs had increased cancer incidence than those from other areas in Korea using regional health data.Standardized incidence ratios (SIR) were calculated using the frequency of cancer cases in the National Cancer Registry of the exposed area (Buki-myeon), Chungcheongbuk-do (Chungbuk, state including Buki-myeon), and whole Korea from 1999 to 2017. A retrospective cohort was created using National Health Insurance System data from 2002 to 2018. The exposed group was defined as those having a residential history in the exposed area. The control group was defined as those having a residential history in nearby towns or counties in Chungbuk, excluding counties having living and cultural areas in other provinces and cities. Hazard ratio (HR) and 95% confidence intervals (CI) were estimated using the Cox proportional hazard model adjusted for age, level of health insurance fee, and smoking history.In the ecological study using National Cancer Registry data, the risk of all cancers, all cancers excluding thyroid, esophageal, stomach, and lung cancers in the exposed area were 1.13 (95% CI 1.03-1.24), 1.15 (95% CI 1.04-1.26), 1.91 (95% CI 1.13-2.89), 1.39 (95% CI 1.14-1.66), and 1.29 (95% CI 1.03-1.57) times higher than in whole Korea among exposed males, respectively. In the retrospective cohort, 4300 males (26,821 person-years) and 3796 females (24,746 person-years) in exposed group, 150,964 males (1,212,010 person-years) and 134,535 females (1,104,025 person-years) in control group were analyzed. After adjusting for several confounding factors, the risks for gallbladder cancer among males and kidney cancer among females were 2.65 (95% CI 1.38-5.06) and 2.82 (95% CI 1.13-7.03) times higher in the exposed group versus the control group, respectively.Cancer risk was higher in Koreans having residential history living near IWIs compared to the other areas. Further study warrants nationwide effects and longer follow-up of WIs for cancers in Korea.

In this study, antioxidant activities of HeukHarang a novel Korean Lectuca sativa L.extracts compair with Red skirt lettuce. The highest total polyphenol contents was 60% ethanol extracts of HeukHarang and total flavonoid contents was 40% ethanol extracts, 84.70 ± 0.11 mg TAE/10 g DW and 63.82 ± 0.09 mg QE/10 g DW, respectively. The highest FRAP activity and PMA were 60% and 80% ethanol extracts of heuharang, 1,876.3 ± 0.01 mM TEAC/10 g DW and 26.2 ± 0.0 mM AAEAC/10 g DW, respectively. Radical scavenging activity also HeukHarang ethanol extracts was higher than Red skirt lettuce. The highest ORAC value was 76.0 ± 0.43 mM TEAC/10 g DWthehd, 100% ethanol extracts of HeukHarang. As a result, the all antioxidant activities of Heuhalang ethanol extracts were higher than that of Red skirt lettuce as a control.

In some patients, coronavirus disease 2019 (COVID-19) is accompanied by loss of smell and taste, and this has been reportedly associated with exposure to air pollutants. This study investigated the relationship between the occurrence of chemosensory dysfunction in COVID-19 patients and air pollutant concentrations in Korea.Information on the clinical symptom of chemosensory dysfunction, the date of diagnosis, residential area, age, and sex of 60,194 confirmed COVID-19 cases reported to the Korea Disease Control and Prevention Agency from January 20 to December 31, 2020 was collected. In addition, the daily average concentration of air pollutants for a week in the patients' residential area was collected from the Ministry of Environment based on the date of diagnosis of COVID-19. A binomial logistic regression model, using age and gender, standardized smoking rate, number of outpatient visits, 24-hour mean temperature and relative humidity at the regional level as covariates, was used to determine the effect of air pollution on chemosensory dysfunction.Symptoms of chemosensory dysfunction were most frequent among patients in their 20s and 30s, and occurred more frequently in large cities. The logistic analysis showed that the concentration of particulate matter 10 (PMHigh concentrations of air pollutants such as PM

Structurally colored materials present potential technological applications including anticounterfeiting tags for authentication due to the ability to controllably manipulate colors through nanostructuring. Yet, no applications of deep learning algorithms, known to discover meaningful structures in data with far-reaching optimization capabilities, to such optical authentication applications involving low-spatial-frequency laser-induced periodic surface structures (LSFLs) have been demonstrated to date. In this work, by fine-tuning one of the lightweight convolutional neural networks, MobileNetV1, we investigate the optical authentication capabilities of the structurally colorized images on metal surfaces fabricated by controlling the orientation of femtosecond LSFLs. We show that the structural color variations due to a broad range of the illumination incident angles combined with both the controlled orientations of LSFLs and differences in features captured in the image make this system suitable for deep learning-based optical authentication.

Oligodendrocytes, myelin-forming cells in the brain, are vulnerable to oxidative stress. Recent work indicates that air pollution causes demyelinating diseases such as multiple sclerosis. However, little is known about the mechanism of toxicity of ultrafine particulate matters (PMs) to oligodendrocytes. Here, we aimed to determine whether oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes (mOLs) are more vulnerable to ultrafine urban PMs (uf-UPs) than other types of brain cells and damage to adult OPCs and mOLs in the mouse brain exposed to uf-UPs. For in vitro experiments, following exposure to various concentrations (2, 20, and 200 &mu, g/mL) of uf-UPs, we measured survival rates, the amount of reactive oxygen species (ROS), and the total antioxidant capacities (TACs) of brain cells isolated from neonatal Sprague-Dawley rats. For animal experiments, after a four-week exposure to a uf-UP suspension (20 &mu, L, 0.4 mg/mL), we enumerated the number of damaged cells and typed damaged cells in the white matter of the cerebellum of uf-UP-exposed mice. MTT assays and Hoechst staining demonstrated that OPCs and mOLs were more vulnerable to uf-UP-induced damage than astrocytes and cortical neurons at 2, 20, and 200 &mu, g/mL of uf-UPs examined in this study (p &lt, 0.05). Damage to OPCs and mOLs depended on uf-UP concentration. DCF assays and DHE staining indicated that the amount of ROS generated in OPCs and mOLs was significantly higher than in other brain cell types (p &lt, 0.05). In contrast, TAC values in OPCs and mOLs were significantly lower than those of other brain cell types (p &lt, 0.05). Fluoro-Jade B (FJB)-positive cells in the cerebellar white matter of the uf-UP-exposed group were significantly greater in number relative to the control group. Double immunofluorescence indicated that FJB-positive cells are NG2-positive adult OPCs and carbon anhydrase II-positive mOLs. Taken together, our findings suggest that oxidative stress induced by uf-UPs in the brain impairs adult OPCs and mOLs, causing demyelination and reducing the capacity for remyelination.

In this study, antioxidant activities of extracts of 12 Korean strawberry cultivars were evaluated and validation of an analytical method for ellagic acid, a marker compound, was carried out. Cultivar 'Josaenghongshim' had the highest total polyphenol and flavonoid contents. In addition, cultivar 'Josaenghongshim' had the highest value and cultivar 'Seolhyang' showing the highest activity. Ellagic acid contents of 'Suhong', 'Okme', and 'Dahong' cultivars were the highest ellagic acid content. Correlation coefficient of the calibration curve was 0.9999, showing very high linearity. The HPLC-DAD method for the quantitation of ellagic acid content showed high linearity at various concentration ranges, with a limit of detection of 2.35 μg/mL. The limit of quantification was 7.13 μg/mL. Relative standard deviations from intra- and inter-day precision were less than 5.13%. Recovery rates of ellagic acid at 10, 50, and 100 μg/mL, respectively, were 99.0-100.1% with RSD values less than 5.30%. These results provide viable information for the validation of antioxidant capacities of 12 cultivars of Korean strawberries.

Retinal fundus images are used to detect organ damage from vascular diseases (e.g. diabetes mellitus and hypertension) and screen ocular diseases. We aimed to assess convolutional neural network (CNN) models that predict age and sex from retinal fundus images in normal participants and in participants with underlying systemic vascular-altered status. In addition, we also tried to investigate clues regarding differences between normal ageing and vascular pathologic changes using the CNN models. In this study, we developed CNN age and sex prediction models using 219,302 fundus images from normal participants without hypertension, diabetes mellitus (DM), and any smoking history. The trained models were assessed in four test-sets with 24,366 images from normal participants, 40,659 images from hypertension participants, 14,189 images from DM participants, and 113,510 images from smokers. The CNN model accurately predicted age in normal participants; the correlation between predicted age and chronologic age was R2 = 0.92, and the mean absolute error (MAE) was 3.06 years. MAEs in test-sets with hypertension (3.46 years), DM (3.55 years), and smoking (2.65 years) were similar to that of normal participants; however, R2 values were relatively low (hypertension, R2 = 0.74; DM, R2 = 0.75; smoking, R2 = 0.86). In subgroups with participants over 60 years, the MAEs increased to above 4.0 years and the accuracies declined for all test-sets. Fundus-predicted sex demonstrated acceptable accuracy (area under curve > 0.96) in all test-sets. Retinal fundus images from participants with underlying vascular-altered conditions (hypertension, DM, or smoking) indicated similar MAEs and low coefficients of determination (R2) between the predicted age and chronologic age, thus suggesting that the ageing process and pathologic vascular changes exhibit different features. Our models demonstrate the most improved performance yet and provided clues to the relationship and difference between ageing and pathologic changes from underlying systemic vascular conditions. In the process of fundus change, systemic vascular diseases are thought to have a different effect from ageing. Research in context. Evidence before this study. The human retina and optic disc continuously change with ageing, and they share physiologic or pathologic characteristics with brain and systemic vascular status. As retinal fundus images provide high-resolution in-vivo images of retinal vessels and parenchyma without any invasive procedure, it has been used to screen ocular diseases and has attracted significant attention as a predictive biomarker for cerebral and systemic vascular diseases. Recently, deep neural networks have revolutionised the field of medical image analysis including retinal fundus images and shown reliable results in predicting age, sex, and presence of cardiovascular diseases. Added value of this study. This is the first study demonstrating how a convolutional neural network (CNN) trained using retinal fundus images from normal participants measures the age of participants with underlying vascular conditions such as hypertension, diabetes mellitus (DM), or history of smoking using a large database, SBRIA, which contains 412,026 retinal fundus images from 155,449 participants. Our results indicated that the model accurately predicted age in normal participants, while correlations (coefficient of determination, R2) in test-sets with hypertension, DM, and smoking were relatively low. Additionally, a subgroup analysis indicated that mean absolute errors (MAEs) increased and accuracies declined significantly in subgroups with participants over 60 years of age in both normal participants and participants with vascular-altered conditions. These results suggest that pathologic retinal vascular changes occurring in systemic vascular diseases are different form the changes in spontaneous ageing process, and the ageing process observed in retinal fundus images may saturate at age about 60 years. Implications of all available evidence. Based on this study and previous reports, the CNN could accurately and reliably predict age and sex using retinal fundus images. The fact that retinal changes caused by ageing and systemic vascular diseases occur differently motivates one to understand the retina deeper. Deep learning-based fundus image reading may be a more useful and beneficial tool for screening and diagnosing systemic and ocular diseases after further development.

Purpose This cross-sectional study aimed to assess the effect of environmental cadmium (Cd) exposure and essential metal imbalance on renal tubular damage and oxidative stress in 979 adults living in a Cd-polluted area near an abandoned copper (Cu) refinery. Methods We analyzed urinary Cd concentrations, renal tubular damage and oxidative stress markers, such as beta-2 microglobulin (β2-MG) and N-acetyl-β-d-glucosaminidase (NAG) activity and urine malondialdehyde (MDA) levels. The serum copper-to-zinc ratio (CZR) was used as an essential metal imbalance indicator. We divided the subjects into two Cd exposure groups based on the reference level of urinary Cd for renal dysfunction (2 μg/g creatinine). Results The geometric mean concentration of urinary Cd in all subjects was 2.25 μg/g creatinine. In both low and high Cd exposure groups, urinary Cd levels were positively correlated with urinary NAG activity, but not with serum CZR. After multivariate adjustment, serum CZR was strongly associated with urinary β2-MG levels in the low Cd exposure group (β = 1.360, P = 0.019) and was significantly associated with urinary MDA levels, regardless of Cd exposure level. In addition, the risk of renal tubular damage was significantly associated with urinary Cd level, particularly in the lowest or highest CZR tertile groups. Conclusions Essential metal imbalance may be a determinant of oxidative stress and renal tubular damage in a chronically Cd-exposed population, and proper zinc supplementation will be effective in preventing adverse health effects due to Cd exposure.