Computational dielectric spectroscopy on solid-solution interface by time-dependent voltage applied molecular dynamics simulation.

A frequency-dependent dielectric constant characterizes the dielectric response of a medium and also represents the time scale of system's collective dynamics. Although it is valuable not only academically but also practically for developing advanced devices, getting the value of a solution at the interface with a solid or electrode surface is challenging both experimentally and computationally. Here, we propose a computational method that imitates the dielectric spectroscopy and AC impedance measurement. It combines a time-dependent voltage applied molecular dynamics simulation with an equivalent circuit representation of a system composed of a solution confined between two identical electrodes. It gives the frequency-dependent dielectric constants of the bulk solution and the interface simultaneously. Unlike the conventional method, it does not require computation of a dipole autocorrelation function and its Fourier transformation. Application of the method on a system of water confined between polarizable Pt electrodes gives the static dielectric constant and the relaxation time of the bulk water in good agreement with previous simulation results and experimental values. In addition, it gives a much smaller static dielectric constant at the interface, consistent with previous observations. The outline of the dielectric dispersion curve of the interface seems similar to that of the bulk, but the relaxation time is several times faster.

Association between habitual snoring and vigilant attention in elementary school children.

OBJECTIVES: Vigilant attention (VA) is a fundamental neurocognitive function. However, the association between habitual snoring (HS) and VA in community-based children remains unclear. Therefore, this study aimed to elucidate the association. METHODS: The study included 2014 children from grades 1-6 across six elementary schools. Snoring frequency was evaluated using a questionnaire administered to parents. VA was assessed using a brief 3-min psychomotor vigilance test (PVT-B). Generalized linear models and multivariate logistic regression analysis were utilized to examine the association between snoring frequency and PVT-B performance. Impaired PVT-B performance was defined as the worst quartile of PVT-B metrics. RESULTS: The PVT-B performance significantly improved with advancing school grade level (p trend < 0.0001). A significant negative correlation was observed between snoring frequency and PVT-B performance. Particularly, in grade 1, HS was associated with a higher risk of impaired PVT-B performance, including response speed (mean reciprocal reaction time) (adjusted odds ratio [aOR] 2.56, 95% confidence interval [CI]: 1.20-5.50), more slowest 10% RT (aOR 3.28, 95% CI: 1.51-6.88), and more lapse500 (number of lapse of reaction time ≥ 500 ms) (aOR 3.18, 95% CI: 1.45-6.80) compared to children without snoring. CONCLUSIONS: Our findings show that VA rapidly improves throughout elementary school. Additionally, younger children with HS are at risk of VA deficits, emphasizing the importance of early intervention for HS.

Self-reported sleep tendency poorly predicts the presence of obstructive sleep apnea in commercial truck drivers.

BACKGROUND AND OBJECTIVES: Drowsy driving increases the risk of motor vehicle crashes in those with untreated obstructive sleep apnea (OSA). Although previous studies indicated that excessive daytime sleepiness (EDS) might not predict OSA, they were not conclusive due to their small study sizes or restricted participants to sleep clinic patients. The overall objective was to determine whether self-reported EDS can be used for case identification of OSA among commercial truck drivers. METHODS: Commercial truck drivers (N = 19,699) were screened for OSA-related symptoms. EDS was determined using the Epworth Sleepiness Scale (ESS) ≥ 11 and all participants completed the home sleep apnea test using a type 4 portable monitor to derive the respiratory event index (REI). Regression analyses were used to characterize the association between EDS and REI. RESULTS: EDS was associated with OSA severity (p for trend <0.001). The sensitivity and specificity values of EDS for identifying moderate-to-severe OSA (REI ≥15 events/hour) were 0.10 and 0.93, respectively, and 0.48 and 0.71 if BMI ≥25 kg/m2 was added. Those using BMI ≥25 kg/m2 with OSA-related signs yielded the best sensitivity and specificity of 0.77 and 0.50, which were not improved by the addition of EDS. CONCLUSIONS: Despite the associations between EDS and OSA severity and between OSA and lethal crash, case-identification of OSA using the ESS in commercial truck drivers is poor. Thus, OSA screening strategy may need a special approach, including a hierarchical combination of screening tools (Swiss Cheese Model approach), and incorporation of home sleep apnea testing.

Evaluation of Correlation between Psychomotor Vigilance Task Scores and Drowsiness Estimation Levels Obtained from Facial Videos.

This paper reports the results of an experiment to evaluate the relationship between results obtained with a drowsiness estimation system we have developed using facial videos and those obtained with the Psychomotor Vigilance Task (PVT), which is a standard index of sleepiness used in sleep medicine. The correlation between PVT scores and the output of the drowsiness estimation system, which outputs drowsiness levels from assigned facial expressions, was calculated using data from 30 subjects. The Spearman's correlation coefficients between the drowsiness estimation results and the PVT mean response time, the slowest 10% response time, and the number of lapses were 0.36 (p <0.001), 0.43 (p <0.001), and 0.40 (p <0.001), respectively. Since this experiment showed a correlation between the drowsiness estimation results and those with PVT, it would seem possible to make specific interventions based on drowsiness estimation results learned from ground-truth drowsiness levels. Such estimation results could help prevent accidents resulting from drowsiness or insufficient vigilance while driving or working.

Snoring, obstructive sleep apnea, and upper respiratory tract infection in elementary school children in Japan.

PURPOSE: Both obstructive sleep apnea (OSA) and the common cold are disorders of the upper respiratory tract, and may be associated. However, studies on the association between OSA and upper respiratory tract infections (URTI) in children are scarce. The aim of this study was to investigate possible associations between snoring, the severity of OSA, and URTI in elementary school children. METHODS: This was a cross-sectional study in a community cohort of elementary school children (first and second graders) in Japan. Information on sleep habits, history of URTI, and OSA risk was obtained from a parental questionnaire. Children underwent overnight tracheal sound recordings from which apnea-hypopnea index was estimated. Multivariable logistic analysis was employed to define the association between snoring, OSA, and URTI ≥ 3 episodes over six months. RESULTS: Of the 922 potential enrollees, 653 children and their parents (71%) agreed to participate in the study. Multivariable-adjusted ORs for URTI were 1.73 (95%CI: 1.16 to 2.59) in children who snored 1 to 4 nights per week and 2.82 (95%CI: 1.26 to 6.28) in snoring ≥ 5 nights per week compared with never snoring (reference). Likewise, subjectively reported louder snoring, as well as objectively defined louder sound levels, were significantly associated with URTI. In addition, OR for URTI in children with an estimated apnea-hypopnea index ≥ 2.0 events/hour was 2.65 (95%CI: 1.32 to 5.31) compared to children with apnea-hypopnea index less than 1.0 events/hour (reference). CONCLUSIONS: Snoring and severity of OSA as measured by nocturnal tracheal sound recordings were associated with increased susceptibility to URTI in elementary school children.

Nocturnal Scratching and Quality of Sleep in Children with Atopic Dermatitis.

Itching due to atopic dermatitis causes sleep disorders in children, but its pathology is unknown. The aim of this study is to investigate nocturnal scratching as an indirect index of itching during sleep and its relationship with depth of sleep in children with atopic dermatitis. Nocturnal scratching was measured in a total of 20 children with atopic dermatitis, using a smartwatch installed with the application Itch Tracker. Depth of sleep was analysed using polysomnography. The severity of atopic dermatitis was scored using Eczema Area and Severity Index (EASI) and Patient-Oriented Eczema Measure (POEM). The number and time of nocturnal scratching measured by Itch Tracker had a significantly positive correlation with EASI scores, whereas POEM scores were not correlated with EASI scores. Mean sleep efficiency was 90.0% and scratching episodes (n = 67) started mainly during the awake stage or light sleep stages. In the scratching episodes that started during sleep stages (n = 34), the sleep stage changed to a lighter one or to the awake stage in 35.5% of episodes. Itch Tracker is applicable to measure nocturnal scratching in children. Nocturnal scratching can deteriorate quality of sleep by changing the sleep stage to a lighter one or to the awake stage.

Interaction between the substrate and probe in liquid metal Ga: experimental and theoretical analysis.

Interaction between two bodies in a liquid metal is an important topic for development of metallic products with high performance. We conducted atomic force microscopy measurements and achieved the interaction between the substrate and the probe in liquid Ga of an opaque and highly viscous liquid. The interaction cannot be accessed with the normal atomic force microscopy, electron microscopy, and beam reflectometry. We performed a theoretical calculation using statistical mechanics of simple liquids by mixing an experimentally derived quantum effect. From both experiment and theory, we found an unusual behaviour in the interaction between the solvophobic substances, which has never been reported in water and ionic liquids. Shapes of the interaction curves between several solvophobic and solvophilic pairs in liquid Ga are also studied.

Down-regulation of stimulator of interferon genes (STING) expression and CD8+ T-cell infiltration depending on HER2 heterogeneity in HER2-positive gastric cancer.

BACKGROUND: HER2 signaling might be involved in the regulation of immune cell activation in the tumor microenvironment (TME) of gastric cancer (GC). However, the relationship between HER2 status and immune cell condition in the HER2-positive GC TME is not clearly understood. METHODS: To investigate the effect of HER2 signaling on the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, which contributes to immune cell activation in the GC TME, we evaluated the associations among the expressions of HER2, cGAS-STING, and the number of CD8+ tumor-infiltrating lymphocytes (TIL) by considering HER2 heterogeneity in HER2-positive GC tissues. We also examined the effect of HER2 signaling on the activation of STING signaling in vitro using human HER2-positive GC cell lines. RESULTS: The expression of HER2 is highly heterogeneous in HER2-positive GC tissues, and we found that the number of CD8+ TIL in HER2 high areas was significantly lower than that in HER2 low areas in HER2-positive GC tissues. Intriguingly, the tumor cell-intrinsic expression of STING, but not cGAS, was also significantly lower in the HER2 high areas than the HER2 low areas in HER2-positive GC tissues. Moreover, in vitro experiments, we demonstrated that the blockade of HER2 signaling increased the expression of STING and its target genes, including IFNB1, CXCL9/10/11, and CCL5, in HER2-positive GC cell lines. CONCLUSIONS: Our results suggest that HER2 signaling might suppress immune cell activation in the GC TME by inhibiting STING signaling in tumor cells in HER2-positive GC.

Collective bending motion of a two-dimensionally correlated bowl-stacked columnar liquid crystalline assembly under a shear force.

Stacked teacups inspired the idea that columnar assemblies of stacked bowl-shaped molecules may exhibit a unique dynamic behavior, unlike usual assemblies of planar disc- and rod-shaped molecules. On the basis of the molecular design concept for creating higher-order discotic liquid crystals, found in our group, we synthesized a sumanene derivative with octyloxycarbonyl side chains. This molecule forms an ordered hexagonal columnar mesophase, but unexpectedly, the columnar assembly is very soft, similar to sugar syrup. It displays, upon application of a shear force on solid substrates, a flexible bending motion with continuous angle variations of bowl-stacked columns while preserving the two-dimensional hexagonal order. In general, alignment control of higher-order liquid crystals is difficult to achieve due to their high viscosity. The present system that brings together higher structural order and mechanical softness will spark interest in bowl-shaped molecules as a component for developing higher-order liquid crystals with unique mechanical and stimuli-responsive properties.

Validity and reliability of the Japanese version of the severity hierarchy score for pediatric obstructive sleep apnea screening.

OBJECTIVE: This study aimed to evaluate the validity and reliability of the Japanese version of the severity hierarchy score (J-SHS) in the screening of pediatric obstructive sleep apnea (OSA) among Japanese community children. METHODS: A total of 922 children from elementary schools in Tokyo were recruited. Their parents completed the J-SHS questionnaire, and the children underwent an overnight Tracheal Sound (TS) recording. The reliability of the J-SHS was assessed by Cronbach's alpha coefficients and Spearman's correlation. Construct validity was determined by factor analysis. The discriminative ability to diagnose OSA was evaluated by constructing ROC curves. RESULTS: Five hundred and seventeen children (51.8% male, mean age 7.1 ± 0.7 years) were included. Cronbach's alpha coefficient was 0.80. Factor analysis resulted in a two-factor structure, with factor loadings all above 0.4. A J-SHS score of >1.88 exhibited a 60% sensitivity, 93% specificity, and an area under the curve (AUC) of 0.78 for detecting an apnea-hypopnea index (AHI) of ≥5/h; a J-SHS score of >2.06 exhibited a 75% sensitivity, 84% specificity and AUC of 0.84 for detecting an AHI of ≥3/h among the children with a snoring frequency above two nights/wk. CONCLUSION: The J-SHS exhibits good performance as a screening tool providing a quick and straightforward approach for identifying Japanese children at risk for OSA.

Accelerated constant-voltage quantum mechanical/molecular mechanical method for molecular systems at electrochemical interfaces.

The structure and electronic properties of a molecule at an electrochemical interface are changed by interactions with the electrode surface and the electrolyte solution, which can be significantly modulated by an applied voltage. We present an efficient self-consistent quantum mechanics/molecular mechanics (QM/MM) approach to study a physisorbed molecule at a metal electrode-electrolyte interface under the constant-voltage condition. The approach employs a classical polarizable double electrode model, which enables us to study the QM/MM system in the constant-voltage ensemble. A mean-field embedding approximation is further introduced in order to overcome the difficulties associated with statistical sampling of the electrolyte configurations. The results of applying the method to a test system indicate that the adsorbed molecule is no less or slightly more polarized at the interface than in the bulk electrolyte solution. The geometry of the horizontally adsorbed molecule is modulated by their electrostatic interactions with the polarizable electrode surfaces and also the interactions with cations attracted toward the interface when the adsorbate is reduced. We also demonstrate that the approach can be used to quantitatively evaluate the reorganization energy of a one electron reduction reaction of a molecule in an electrochemical cell.

Clinical outcomes of laparoscopic and endoscopic cooperative surgery for gastric gastrointestinal stromal tumor.

BACKGROUND: Laparoscopic and endoscopic cooperative surgery (LECS) is a well-recognized surgical procedure for gastric gastrointestinal stromal tumor (GIST). In this report, we describe the clinical outcomes of LECS procedures for gastric GIST in our institution. METHODS: We performed LECS procedures, including classical LECS, inverted LECS, closed LECS, and combination of laparoscopic and endoscopic approaches to neoplasia with non-exposure technique (CLEAN-NET), in 40 gastric intraluminal and intramural type GIST patients, whose tumors were ≤ 50 mm in diameter, between September 2012 and December 2020. The patient background, surgical outcomes, postoperative morbidity and mortality, as well as the tumors' clinicopathological characteristics were analyzed retrospectively. RESULTS: Pathological findings showed that most patients had a low or very low risk of tumor recurrence, while one patient had a high risk according to the modified-Fletcher's classification. The median length of postoperative hospital stay was 7 days. Only one patient had severe postoperative grade III complications according to the Clavien-Dindo (C-D) classification, after closed LECS, but was treated successfully with endoscopic hemostasis for postoperative hemorrhage. The remaining patients treated with LECS did not have severe complications. During the follow-up period (median, 31 months), all patients were disease-free, with no tumor recurrence or metastases. CONCLUSION: LECS is a safe surgical procedure for gastric intraluminal and intramural type GIST ≤ 50 mm in diameter, with good clinical outcomes.

Two cases of pancreaticoduodenal aneurysm with median arcuate ligament syndrome treated with coil embolization and median arcuate ligament incision.

Median arcuate ligament syndrome is a clinical condition in which the median arcuate ligament causes compression and narrowing of the celiac artery. It has been reported that collateral pathways, which is developed by the decrease of blood flow from the celiac artery, facilitates the formation of aneurysms. Aneurysms around the pancreas in particular require aggressive therapeutic intervention, because a rupture can be fatal. We herein report two cases of pancreaticoduodenal aneurysms associated with median arcuate ligament syndrome treated by coil embolization and median arcuate ligament incision. Case 1 required a hybrid procedure in which median arcuate ligament incision and coil embolization were performed simultaneously. In Case 2, the median arcuate ligament incision was performed about 3 months after emergency endovascular hemostasis for hemorrhagic duodenal ulcer. In both cases, there were no major postoperative complications and no recurrence of aneurysm. Median arcuate ligament incision may be effective to prevent organ ischemia and aneurysm recurrence after coil embolization of intra-abdominal aneurysms associated with median arcuate ligament syndrome.

Preoperative bacterial culture can predict severe pneumonia in patients receiving esophagectomy.

BACKGROUND: Postoperative pneumonia is one of the major complications after esophagectomy. The aim of this study was to determine whether bacterial cultures before esophagectomy could predict occurrence of postoperative pneumonia and help treatment strategies for postoperative pneumonia. METHODS: Sixty-nine patients who underwent subtotal esophagectomy at Fukushima Medical University Hospital between January 2017 and May 2021 were included in this study. We collected sputum, oral, and/or nasopharyngeal swabs for bacterial culture preoperatively from all patients and from those who were suspected of postoperative pulmonary infections. We compared cultured pathogenic bacteria obtained preoperatively and postoperatively from patients who developed postoperative pneumonia, and investigated their association with incidence of postoperative pneumonia. RESULTS: Postoperative pneumonia occurred in 22 of 69 patients (31%), including 13 cases of severe pneumonia with a Clavien-Dindo classification of grade IIIa or higher. Multivariate analysis revealed that longer operative duration (for 30 minutes increase;odds ratio 1.27, 95% CI 1.01-1.51, p=0.039) and positivity for preoperative bacterial culture (odds ratio 5.03, 95% CI 1.31-19.2, p=0.018) were independent risk factors for severe postoperative pneumonia, but not for all incidences of postoperative pneumonia. Of note, in only 5 of the 22 patients with pneumonia, the same pathogenic species were detected preoperatively and after the onset of pneumonia. CONCLUSIONS: Our results imply that preoperative bacterial culture may be useful to predict severe postoperative pneumonia. However, it may not be useful in determining pathogenic bacteria responsible for postoperative pneumonia.

Effect of hyperhomocysteinemia on a murine model of smoke-induced pulmonary emphysema.

Hyperhomocysteinemia was reported to enhance endoplasmic reticulum (ER) stress and subsequent apoptosis in several cells. However, the precise mechanisms of smoking susceptibility associated with hyperhomocysteinemia has not been fully elucidated. This study included 7- to 9-week-old C57BL6 male mice induced with hyperhomocysteinemia and were exposed to cigarette smoke (CS). A549 cells (human alveolar epithelial cell line) were cultured with homocysteine and were exposed to cigarette smoke extract (CSE) to observe cell viability and expression of proteins related to the ER stress. After 6 months of CS exposure, pulmonary emphysema was more severely induced in the group under the condition of hyperhomocysteinemia compared to that in the control group. The apoptotic A549 cells increased as homocysteine concentration increased and that was enhanced by CSE. Protein expression levels of ER stress markers were significantly increased after simultaneous stimulation. Notably, vitamin B12 and folate supplementation improved ER stress after simultaneous stimulation of A549 cells. In this study, we showed that hyperhomocysteinemia exacerbates CS exposure-induced emphysema in mice, suggesting that hyperhomocysteinemia and CS stimulation enhance ER stress and subsequent induced apoptosis in alveolar epithelial cells. It was suggested that there is a synergistic effect between homocysteine and CS.

Unified polarizable electrode models for open and closed circuits: Revisiting the effects of electrode polarization and different circuit conditions on electrode-electrolyte interfaces.

A precise understanding of the interfacial structure and dynamics is essential for the optimal design of various electrochemical devices. Herein, we propose a method for classical molecular dynamics simulations to deal with electrochemical interfaces with polarizable electrodes under the open circuit condition. Less attention has been given to electrochemical circuit conditions in computation despite being often essential for a proper assessment, especially comparison between different models. The present method is based on the chemical potential equalization principle, as is a method developed previously to deal with systems under the closed circuit condition. These two methods can be interconverted through the Legendre transformation so that the difference in the circuit conditions can be compared on the same footing. Furthermore, the electrode polarization effect can be correctly studied by comparing the present method with conventional simulations with the electrodes represented by fixed charges, since both of the methods describe systems under the open circuit condition. The method is applied to a parallel-plate capacitor composed of platinum electrodes and an aqueous electrolyte solution. The electrode polarization effects have an impact on the interfacial structure of the electrolyte solution. We found that the difference in circuit conditions significantly affects the dynamics of the electrolyte solution. The electric field at the charged electrode surface is poorly screened by the nonequilibrium solution structure in the open circuit condition, which accelerates the motion of the electrolyte solution.

Visualization of Topological Pharmacophore Space with Graph Edit Distance.

A topological pharmacophore (TP) is a chemical graph-based pharmacophore representation, where nodes are pharmacophoric features (PF) and edges are topological distances between PFs. Previously proposed sparse pharmacophore graphs (SPhGs) for TPs were shown to be effective in identifying structurally different active compounds while maintaining the interpretability of the graphs. However, one limitation of using SPhGs as queries is that many structurally similar SPhGs can be identified from a set of active compounds, requiring the classification and visualization of SPhGs, followed by an understanding of the pharmacophore hypotheses. In this study, we propose a scheme for SPhG analysis based on dimensionality reduction techniques with the graph edit distance (GED) metric. This metric enables measuring similarities among SPhGs in a quantitative manner. The visualization of SPhGs, which themselves are the graphs shared by active compounds, can help us understand the pharmacophore hypotheses as well as the data set. As a proof-of-concept study, we generated two-dimensional SPhG-maps using three dimensionality reduction techniques for six biological targets. A comparison with other pharmacophore representations was also conducted. We demonstrated knowledge extraction (interpretation of the data set) from the generated maps. Our findings include a suitable mapping algorithm as well as a pharmacophore hypothesis analysis procedure using an SPhG-map.

Incidence of upper extremity deep vein thrombosis in the retrosternal reconstruction after esophagectomy.

BACKGROUND: Upper extremity deep vein thrombosis (UEDVT) is relatively rare but cannot be negligible because it can cause fatal complications. Although it is reported that the occurrence rate of UEDVT has increased due to central venous catheter (CVC), cancer, and surgical invasion, there is still limited information for esophagectomy. The aim of this study was to evaluate the clinical factors, including CVC placement and thromboprophylaxis approach, as well as retrosternal space's width as a predictive factor for UEDVT in patients receiving esophagectomy. METHODS: This study included 66 patients who underwent esophagectomy with retrosternal reconstruction using a gastric tube. All patients routinely underwent contrast-enhanced computed tomography (CT) on the 4th postoperative day. Low-molecular-weight-heparin (LMWH) was routinely administered by the 2nd postoperative day. To evaluate retrosternal space's width, (a) The distance from sternum to brachiocephalic artery and (b) the distance from sternum to vertebra were measured by preoperative CT, and the ratio of (a) to (b) was defined as the width of retrosternal space. RESULTS: Among all patients, 11 (16.7%) suffered from UEDVT, and none was preoperatively received CVC placement, while 7 were inserted in non-UEDVT cases. Retrosternal space's width in patients with UEDVT was significantly smaller than that in patients without UEDVT (0.17 vs. 0.26; P < 0.0001). A cutoff value of the width was 0.21, which has high sensitivity (87%) and specificity (82%) for UEDVT prediction, respectively. CONCLUSION: The existence of CVC may not affect the development of UEDVT, but preoperative evaluation of retrosternal ratio may predict the occurrence of UEDVT.

Role of CC Chemokine Ligand 17 in Mouse Models of Chronic Obstructive Pulmonary Disease.

Lung function deterioration is significantly associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). We previously reported that CC chemokine ligand 17/thymus and activation-regulated chemokine (CCL17/TARC) could be a predictive factor of lung function decline in patients with COPD. However, the role of CCL17 in the pathogenesis of COPD is unclear. Here we examined the role of CCL17 in lung inflammation using mouse COPD models. Exposure to cigarette smoking induced CCL17 production in bronchial epithelial cells and accumulation of alveolar macrophages in the lungs. Intranasal administration of recombinant CCL17 further enhanced cigarette smoke-induced macrophage accumulation and also aggravated elastase-induced pulmonary emphysema. We confirmed that cigarette smoke (CS) extract as well as hydrogen peroxide upregulated CCL17 in BAES-2B cells. Of note, macrophages of both M1 and M2 surface markers were accumulated by cigarette smoke. Both alveolar macrophage accumulation via exposure to cigarette smoking and emphysematous changes induced by elastase administration were significantly reduced in CCL17-deficient mice. We further demonstrated that CCL17 strongly induced the expression of CC chemokine ligand 2 (CCL2), a chemoattractant for macrophages, in RAW264.7 cells, and its production was inhibited by knockdown of CCR4, the receptor of CCL17. Collectively, the present results demonstrate that CCL17 is produced by lung epithelial cells upon CS exposure. Furthermore, CCL17 is involved in CS-induced accumulation of alveolar macrophages and development of elastase-induced pulmonary emphysema, possibly through CCL17-induced production of CCL2 by macrophages. Our findings may provide a new insight into the pathogenesis of COPD.