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Jong Geol Jang, Jin Hong Chung, Kyeong-Cheol Shin, Hyun Jung Jin, Kwan Ho Lee, June Hong Ahn Department of Internal Medicine, Division of Pulmonology and Allergy, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, Republic of KoreaCorrespondence: Kwan Ho Lee; June Hong AhnDepartment of Internal Medicine, Division of Pulmonology and Allergy, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, 170 Hyeonchung-ro, Namgu, Daegu, 42415, Republic of KoreaTel +82-53-640-6601; +82-53-640-6577Fax +82-53-620-3849Email ghlee@med.yu.ac.kr; fireajh@gmail.comObjective: Critical inhaler handling errors are associated with an increased risk of adverse outcomes in patients with chronic obstructive pulmonary disease (COPD). However, real-world data on inhaler device handling techniques and the risk factors for critical inhaler errors in the Asian population have been examined in only a few studies. We evaluated the rates and risk factors for critical inhaler errors in the COPD population in Korea.Methods: COPD patients were prospectively enrolled from January 2018 to November 2019. An advanced practice nurse evaluated their inhaler technique. The 308 inhalers used by the 261 participants in this study included dry powder inhalers (DPIs; Turbuhaler, Breezhaler, Ellipta, Diskus, Genuair), a soft mist inhaler (SMI; Respimat), and pressurized metered dose inhalers (pMDIs).Results: The percentage critical errors for Turbuhaler, Breezhaler, Ellipta, Diskus, Genuair, Respimat, and pMDI usage were 60.0%, 41.0%, 27.8%, 12.5%, 44.4%, 45.5%, and 55.0%, respectively. In the multivariate analyses, female sex, short COPD duration, dissatisfaction with the inhaler (assessed by FSI-10), and moderate acute exacerbations (AEs) in the prior year were independent risk factors for any critical error in the DPI group. In the SMI group, a low education level and frequent AEs in the prior year were independent risk factors for any critical error, whereas a high COPD assessment test (CAT) score was the only risk factor in the pMDI group.Conclusion: Critical inhaler errors are common among patients with COPD, regardless of their preferred inhaler device. The rates and risk factors for critical inhaler errors differed among patients using different devices. Optimal device selection considering the risk factors of inhaler misusage will improve disease control in COPD patients.Keywords: COPD, inhalation therapy, error, risk factor

Joon Young Choi,1 Hyoung Kyu Yoon,2 Kyeong-Cheol Shin,3 So-Young Park,4 Chang Youl Lee,5 Seung Won Ra,6 Ki Suck Jung,7 Kwang Ha Yoo,4 Chang-Hoon Lee,8 Chin Kook Rhee9 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 3Division of Pulmonology and Allergy, Regional Center for Respiratory Disease, Yeungnam University Medical Center, Daegu, Republic of Korea; 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chuncheon Sacred Heart Hospital, Hallym University Medical Center, Chuncheon, Republic of Korea; 6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea; 7Division of Pulmonary Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University Medical School, Anyang, Republic of Korea; 8Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaCorrespondence: Chin Kook RheeDivision of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodaero, Seochogu, Seoul 06591, Republic of KoreaTel +82 2 2258 6067Fax +82 2 599 3589Email chinkook77@gmail.comPurpose: Previous studies have used various definitions to classify chronic obstructive pulmonary disease (COPD) patients into chronic bronchitis (CB) and non-CB patients. This study was performed to identify differences among three definitions of CB based on the classical method, St. George’s Respiratory Questionnaire (SGRQ), and the CAT (COPD Assessment Test) score.Patients and methods: We extracted data from the multicenter Korea COPD Subgroup Study (KOCOSS) cohort, for which patients recruited from among 47 medical centers in South Korea beginning in April 2012. Patients were classified according to three different definitions of CB: 1) classical definition; 2) SGRQ (using questions regarding cough and sputum); and 3) CAT score (comprising cough [CAT1] and sputum [CAT2] subscale scores).Results: A total of 2694 patients were enrolled in this study. The proportions of CB were 10.8%, 35.8%, and 24.0% according to the classical, SGRQ, and CAT definitions, respectively. The three definitions yielded consistently significant differences between CB and non-CB patients in modified Medical Research Council dyspnea scale CAT score, SGRQ score, number of moderate-to-severe exacerbations per year and forced expiratory volume in 1 second. By three definitions, CB consistently predicted future risk of exacerbation. The kappa coefficient of agreement between the classical definition and SGRQ definition was 0.29, that of the classical definition and CAT definition was 0.32, and that of the SGRQ definition and CAT definition was 0.44.Conclusion: Patients with CB according to the new definitions based on SGRQ or CAT score showed similar clinical characteristics to those defined according to the classical definition. The new CB definitions may be used as alternatives to the classical definition.Keywords: chronic bronchitis, CAT score, SGRQ score, chronic obstructive pulmonary disease, KOCOSS database

June Hong Ahn, Jin Hong Chung, Kyeong-Cheol Shin, Eun Young Choi, Hyun Jung Jin, Mi Suk Lee, Mi Jeong Nam, Kwan Ho Lee Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, College of Medicine, Yeungnam University, Daegu, South KoreaCorrespondence: Kwan Ho LeeDivision of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, 170 Hyunchung-Ro, Nam-Gu, Daegu 42415, South KoreaEmail ghlee@med.yu.ac.krObjective: Chronic obstructive pulmonary disease (COPD) acute exacerbations are significant causes of morbidity and mortality. “Frequent exacerbator” phenotypes are considered a distinct subgroup and this phenotype has a negative effect on lung function, quality of life, activity, hospital admission, and mortality. We assess inhaler handling technique and adherence, and evaluate risk factors associated with frequent exacerbations in COPD patients.Methods: This study was a cross-sectional, case-control study. We prospectively enrolled 189 COPD patients from Yeungnam University Hospital from January 2018 to November 2018. Subjects were tested regarding their inhaler technique in face-to-face interviews with an advanced practice nurse of inhaler upon study entry. Frequency of moderate to severe COPD exacerbations were reviewed via electronic medical records during 12 months prior to study entry. Frequent exacerbations were defined as ≥2 moderate to severe exacerbations in the prior 12 months. Multivariate logistic regression was performed to identify risk factors for frequent exacerbations.Results: Among 189 COPD patients, 50 (26.5%) were frequent exacerbators. Based on univariate analyses, body mass index (BMI) < 25 kg/m2, lower forced expiratory volume in 1 s (FEV1), higher mMRC, lower feeling of satisfaction with the inhaler, and any critical errors were potential risk factors for frequent exacerbations. Multivariate logistic regression analyses revealed that BMI < 25 kg/m2 (OR, 2.855, 95% CI, 1.247–6.534; p=0.013), higher mMRC (OR, 1.625, 95% CI, 1.072–2.463; p=0.022), and any critical error (OR, 2.020, 95% CI, 1.021–3.999; p=0.044) were risk factors.Conclusion: Any critical error, BMI < 25 kg/m2 and high mMRC are independent risk factors for frequent exacerbations in COPD patients. Careful monitoring and education around inhaler devices, particularly in frequent exacerbators, are important components of COPD treatment.Keywords: COPD, inhalation therapy, drug use error, disease exacerbation

Jong Geol Jang,1 Jee Seon Kim,2 Jin Hong Chung,1 Kyeong Cheol Shin,1 June Hong Ahn,1 Mi Sook Lee,3 So Hee Bang,3 Da Yeong Park,3 Mee Jung Nam,3 Hyun Jung Jin,1,* Kwan Ho Lee1,* 1Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, College of Medicine, Daegu, Republic of Korea; 2Department of Internal Medicine, Semyeong Christianity Hospital, Pohang, Republic of Korea; 3Department of Education and Management Services, Yeungnam University Medical Center,College of Medicine, Daegu, Republic of Korea*These authors contributed equally to this workCorrespondence: Hyun Jung JinDivision of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Republic of KoreaTel +82-53-640-6578Fax +82-53-640-6449Email jhj0619@yu.ac.krBackground: Despite the increasing prevalence of chronic obstructive pulmonary disease (COPD) worldwide, knowledge and awareness of COPD remain extremely low. This prospective study aimed to demonstrate the effectiveness of organized educational intervention.Patients and methods: The study participants included patients diagnosed with COPD and receiving inhaler treatment. In this prospective study, the patients made three sequential visits to the hospital (baseline, 1 month, 3 months). On their first and second visits, patients received systematic education about COPD. On their first and third visits, each patient was evaluated using a COPD Assessment Test, COPD Knowledge Questionnaire, Hospital Anxiety and Depression Scale, and Rosenberg Self-Esteem Scale.Results: Fifty-five participants were enrolled in the study. The mean COPD knowledge score before and after education was 12.51±3.19 and 17.89±1.37, respectively, indicating a significant increase in the score post-education (P

Hye Sook Choi,1 Yong Bum Park,2,3 Kyeong Cheol Shin,4 Seung Hun Jang,3,5 Kang Hyeon Choe,6 Young Sam Kim,7 Sun Young Kyung,8 Sung Ho Yoon,9 Ju Sang Kim,10 Sung Soo Jung11 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, Republic of Korea; 2Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital-Kangdong, Seoul, Republic of Korea; 3Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea; 4Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Hospital, Daegu, Republic of Korea; 5Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea; 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Republic of Korea; 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yonsei University Health System, Seoul, Republic of Korea; 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea; 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chosun University Hospital, Gwangju, Republic of Korea; 10Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, The Catholic University, Incheon St Mary’s Hospital, Incheon, Republic of Korea; 11Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea Background and objective: The Exacerbations of Chronic Obstructive Pulmonary Disease Tool-Patient-Reported Outcomes (EXACT-PRO) has been suggested as a reliable and valid measure for early assessment of COPD exacerbations and perceived recovery. However, there has been no evidence for EXACT-PRO efficacy in assessing recovery from treatment in a randomized controlled trial. The study evaluated the reliability, validity, and responsiveness of EXACT-PRO for the evaluation of the efficacy of acute treatment in patients with COPD exacerbation.Methods: In a Phase III randomized controlled study for assessing the efficacy of antibiotic treatment on COPD exacerbation, EXACT-PRO was evaluated in the responders and non-responders.Results: A total of 295 patients were analyzed (259 responders and 37 non-responders). Cronbach’s α was 0.96 for EXACT total, 0.96 for the breathlessness domain, 0.89 for the cough and sputum domain, and 0.93 for the chest symptoms domain. The EXACT score correlated with the COPD assessment test (CAT) score (r=0.8, P

Hye Sook Choi,1 Ju Ock Na,2 Jong Deog Lee,3 Kyeong-Cheol Shin,4 Chin Kook Rhee,5 Yong Il Hwang,6 Seong Yong Lim,7 Kwang Ha Yoo,8 Ki Suck Jung,6 Yong Bum Park9 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyunghee University Hospital, Seoul, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Pulmonary Medicine, Soonchunhyang University Cheonan Hospital, Cheonan-si, Republic of Korea; 3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Gyeongsang National University, Jinju, Republic of Korea; 4Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Yeungnam University Hospital, Daegu, Republic of Korea; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea; 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea; 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University Medical Center, Seoul, Republic of Korea; 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea Background: The 2017 GOLD guidelines revised assessment of COPD by eliminating the FEV1 criterion.Aim: First, we explored the redistribution of 2011 GOLD groups by reference to the 2017 GOLD criteria. Second, we investigated the characteristics of GOLD B patients and the natural course of GOLD B patients according to the 2017 GOLD guidelines.Methods: In total, 2,010 COPD patients in the Korean COPD Subgroup Study cohort were analyzed at baseline and 1 year after enrollment.Results: The 2011 GOLD C patients were redistributed to the 2017 A (64.5%) and C (35.4%) groups. The 2011 GOLD D patients were redistributed to the 2017 B (61.6%) and D (38.6%) groups. The GOLD B patients constituted 62.7% of all patients according to the 2017 classification. Such patients exhibited higher % predicted FEV1 values, longer six-minute walk distances, fewer symptoms, and lower inflammatory marker levels than GOLD D patients. Most GOLD B patients remained in that group (69.1%), but 13.8% progressed to group D at 1-year follow-up. The factors associated with progression from GOLD B to GOLD D were older age, higher modified Medical Research Council (mMRC) and St George’s Respiratory Questionnaire (SGRQ) symptom scores, and a lower % predicted FEV1 value.Conclusion: Severe symptoms, poorer health status, and greater airflow limitation increased patients’ risk of exacerbation and progression from group B to group D when the 2017 GOLD criteria were applied. Keywords: COPD, GOLD B, progression

Dong-Won Lee,1 Hyun-Jung Jin,2 Kyeong-Cheol Shin,2 Jin-Hong Chung,2 Hyoung-Woo Lee,3 Kwan-Ho Lee2 1Division of Pulmonology, Department of Internal Medicine, Andong Sungso Hospital, Andong, 2Division of Pulmonology and Allergy, 3Division of Endocrinology, Department of Internal Medicine, Yeungnam University Hospital, Daegu, South Korea Background: Sarcopenia and decreased bone-mineral density (BMD) are common in elderly people, and are major comorbidities of obstructive airway disease (OAD). However, the relationship between sarcopenia and BMD in each OAD phenotype, especially asthma–COPD overlap syndrome (ACOS), is not yet clear. We aimed to evaluate differences in BMD according to the presence of sarcopenia in each OAD phenotype. Materials and methods: Among the research subjects in KNHANES IV and V (2008–2011), 5,562 were ≥50 years old and underwent qualified spirometry and dual-energy X-ray absorptiometry. A total of 947 subjects were included in the study: 89 had asthma, 748 COPD, and 110 ACOS. Results: In the COPD and ACOS phenotypes, T-scores were lower in the sarcopenia group than the nonsarcopenia group. Prevalence rates of osteopenia and osteoporosis were higher in the sarcopenia group than the nonsarcopenia group. (P

Joon Young Choi,1 Hyoung Kyu Yoon,2 Seoung Ju Park,3 Yong Bum Park,4 Kyeong-Cheol Shin,5 Ju Ock Na,6 Kwang Ha Yoo,7 Ki-Suck Jung,8 Young Kyoon Kim,1 Chin Kook Rhee1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 3Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, 4Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, 5Regional Center for Respiratory Disease, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, 6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, 8Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, Republic of Korea Background: The chronic bronchitis (CB) phenotype has been associated with poor quality of life and an increased risk of disease in patients with COPD. However, little information exists regarding the relationship between the CB phenotype and the COPD assessment test (CAT) score. The goal of this study was to reveal the different pattern of CAT scores between CB and non-CB patients. Moreover, we aimed to investigate whether the CB phenotype is an independently associated factor for more symptom and high-risk groups.Methods: Data were obtained from the Korea COPD Subgroup Study cohort recruited from 46 centers in South Korea since April 2012. CB patients were defined as having a chronic cough and sputum for 3 months per year, for a period of 2 consecutive years. We investigated the pattern of CAT and subquestionnaire scores between CB and non-CB patients. We also analyzed the proportion of CB phenotypes in each Global initiative for chronic Obstructive Lung Disease (GOLD) stage. Finally, we performed a logistic regression analysis to identify whether the CB phenotype was an independently associated factor for more symptom and high-risk groups.Results: Of the 1,106 study patients, 11.5% of patients were found to have a CB phenotype. CB phenotypes were most common in GOLD III (GOLD 2006) and GOLD D (GOLD 2015) stages. CAT scores were significantly higher in CB patients not only in terms of the total score but also for each subquestionnaire. Logistic regression revealed that the CB phenotype is an independently associated factor for more symptom and high-risk groups.Conclusion: The present study revealed that CB patients have higher CAT scores and subquestionnaire results compared to non-CB patients. Additionally, we demonstrated that the CB phenotype is an independently associated factor for both more symptom and high-risk groups. Keywords: chronic obstructive pulmonary disease, chronic bronchitis, COPD assess­ment test

Chin Kook Rhee,1 Jin Woo Kim,2 Yong Il Hwang,3 Jin Hwa Lee,4 Ki-Suck Jung,3 Myung Goo Lee,5 Kwang Ha Yoo,6 Sang Haak Lee,7 Kyeong-Cheol Shin,8 Hyoung Kyu Yoon9 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Uijeongbu St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, 3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul, 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, 7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 8Regional Center for Respiratory Disease, Yeungnam University Medical Center, Yeungnam University College of Medicine, Daegu, 9Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea Background and objective: According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, either a modified Medical Research Council (mMRC) dyspnea score of ≥2 or a chronic obstructive pulmonary disease (COPD) assessment test (CAT) score of ≥10 is considered to represent COPD patients who are more symptomatic. We aimed to identify the ideal CAT score that exhibits minimal discrepancy with the mMRC score.Methods: A receiver operating characteristic curve of the CAT score was generated for an mMRC scores of 1 and 2. A concordance analysis was applied to quantify the association between the frequencies of patients categorized into GOLD groups A–D using symptom cutoff points. A κ-coefficient was calculated.Results: For an mMRC score of 2, a CAT score of 15 showed the maximum value of Youden’s index with a sensitivity and specificity of 0.70 and 0.66, respectively (area under the receiver operating characteristic curve [AUC] 0.74; 95% confidence interval [CI], 0.70–0.77). For an mMRC score of 1, a CAT score of 10 showed the maximum value of Youden’s index with a sensitivity and specificity of 0.77 and 0.65, respectively (AUC 0.77; 95% CI, 0.72–0.83). The κ value for concordance was highest between an mMRC score of 1 and a CAT score of 10 (0.66), followed by an mMRC score of 2 and a CAT score of 15 (0.56), an mMRC score of 2 and a CAT score of 10 (0.47), and an mMRC score of 1 and a CAT score of 15 (0.43).Conclusion: A CAT score of 10 was most concordant with an mMRC score of 1 when classifying patients with COPD into GOLD groups A–D. However, a discrepancy remains between the CAT and mMRC scoring systems. Keywords: COPD, CAT, mMRC, concordance, discrepancy

Surveillance is an important component of influenza control. This report describes the establishment and first results of the Korean Influenza Surveillance Scheme (KISS), an integrated clinical and laboratory surveillance network involving 622 public health centres (PHCs) and private clinics. Sentinel physicians reported cases of influenza-like illness (ILI) weekly and forwarded specimens for virus isolation and characterization. Influenza activity during the opening 2000-2001 season was milder and delayed compared with previous years. The ILI consultation rate corresponded well with the number of influenza virus isolates, both peaking in week 10 of 2001. Influenza A(H3N2) was the dominant isolate. The peak ILI consultation rate was higher in private clinics than in PHCs (5.04 vs 1.79 cases/1000 visits). An evaluation questionnaire generated potential enhancements to the scheme. KISS appears to represent the pattern of influenza activity accurately and will have a valuable role in monitoring and preventing epidemics in Korea. [ABSTRACT FROM AUTHOR]

Background: Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients., Methods: This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV 1 /FVC) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score., Results: In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV 1 , and FEV 1 /FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported., Conclusion: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks., (© 2024. The Author(s).)

The brain contains the highest concentration of cholesterol in the human body, which emphasizes the importance of cholesterol in brain physiology. Cholesterol is involved in neurogenesis and synaptogenesis, and age-related reductions in cholesterol levels can lead to synaptic loss and impaired synaptic plasticity, which potentially contribute to neurodegeneration. The maintenance of cholesterol homeostasis in the neuronal plasma membrane is essential for normal brain function, and imbalances in cholesterol distribution are associated with various neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. This review aims to explore the molecular and pathological mechanisms by which cholesterol imbalance can lead to neurotransmission defects and neurodegeneration, focusing on four key mechanisms: (1) synaptic dysfunction, (2) alterations in membrane structure and protein clustering, (3) oligomers of amyloid beta (Aβ) protein, and (4) α-synuclein aggregation., (© 2024. The Author(s).)

Rhabdomyosarcoma 2-associated transcript (RMST) long non-coding RNA has previously been shown to cause Kallmann syndrome (KS), a rare genetic disorder characterized by congenital hypogonadotropic hypogonadism (CHH) and olfactory dysfunction. In the present study, we generated large deletions of approximately 41.55 kb in the RMST gene in human pluripotent stem cells using CRISPR/Cas9 gene editing. To evaluate the impact of RMST deletion, these cells were differentiated into hypothalamic neurons that include 10-15% neurons that express gonadotrophin-releasing hormone (GnRH). We found that deletion in RMST did not impair the neurogenesis of GnRH neurons, however, the hypothalamic neurons were electro-physiologically hyperactive and had increased calcium influx activity compared to control. Transcriptomic and epigenetic analyses showed that RMST deletion caused altered expression of key genes involved in neuronal development, ion channels, synaptic signaling and cell adhesion. The in vitro generation of these RMST-deleted GnRH neurons provides an excellent cell-based model to dissect the molecular mechanism of RMST function in Kallmann syndrome and its role in hypothalamic neuronal development., (© 2024. The Author(s).)

Background: Acute bronchitis is the most common respiratory disease. Mixture of Ivy Leaf Extract and Coptidis rhizome syrup has shown good treatment efficacy against chronic bronchitis and acute respiratory infections. This study aimed to evaluate the efficacy and safety of Mixture of Ivy Leaf Extract and Coptidis rhizome compared with those of Pelargonium sidoides extract, for the treatment of acute bronchitis., Methods: We performed a multicenter, randomized, double-blind, active-controlled, parallel phase III study in 220 patients with acute bronchitis. The participants were offered either Mixture of Ivy Leaf Extract and Coptidis rhizome syrup (AGS) and placebo of P. sidoides tablet or placebo syrup and active tablet of P. sidoides (AGU) for 7 days. The primary endpoint was the change in the Bronchitis Severity Score (BSS) from the baseline visit (visit 2) to day 7 (visit 3)., Results: For the primary outcome, there was no significant difference in the change of total BSS between visits 2 and 3 (-4.10 ± 1.93 vs. -4.24 ± 1.85, p  = 0.5125), and since the upper limit of the confidence interval (1.00) was smaller than the predetermined non-inferiority margin (1.17), it was confirmed that the AGS group was non-inferior to the AGU group. The changes in each symptom in the BSS between visits 2 and 3 also showed no significant differences. The overall improvement rate measured by the investigator (91.7 vs. 89.7%; p  = 0.3506) and the satisfaction rate of the participants at visit 3 also showed no significant differences (97.2 vs. 94.4%; p  = 0.4388). Regarding safety issues, adverse reactions were noted in both groups similarly, with no serious adverse events (4.55 vs. 3.64%, p  > 0.999)., Conclusion: Mixture of Ivy Leaf Extract and Coptidis rhizome syrup is as effective and safe as P. sidoides in controlling symptoms of acute bronchitis.

Unlike natural soyasaponins and their aglycones formed by enzymatic hydrolysis in the human intestine, in vivo intermediate soyasaponin metabolites are difficult to prepare. Therefore, the pharmacological activities of in vivo intermediate soyasaponins remain uninvestigated. Herein, in vivo intermediate soyasaponins with purities of >90% were prepared by in vitro deacetylation (alkaline treatment) and deglucosylation (β-glucosidase treatment) of natural soyasaponins using preparative high-performance liquid chromatography. These compounds exhibited higher anti-inflammatory and antioxidant activities than natural soyasaponins in in vitro bioassays, suggesting that the intermediate soyasaponins can be used as improved bioactive food supplements. To the best of our knowledge, this is the first study reporting the in vitro preparation and bioassays of in vivo intermediate soyasaponin metabolites formed in the human intestine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The PACIFIC trial demonstrated survival benefit of durvalumab after concurrent chemoradiotherapy (CCRT) in unresectable stage III non-small-cell lung cancer. Data on the effectiveness and safety of durvalumab in elderly patients is lacking., Methods: This retrospective study was conducted between September 2017 and September 2022. Progression-free survival (PFS), overall survival (OS), recurrence patterns, first subsequent treatment after recurrence, factors associated with survival outcomes, and adverse events (AEs) were compared., Results: Of the 286 patients, 120 (42.0%) were ≥ 70 years and 166 (58.0%) were < 70 years. The median PFS (17.7 vs. 19.4 months; P = .43) and median OS (35.7 months vs. not reached; P = .13) were similar between 2 groups. Proportion of patients who completed durvalumab was lower in elderly patients (27.5% vs. 39.2%; P = .040). In elderly patients, ECOG PS 0 or 1 was associated with better PFS, and being male and having received a cisplatin-based regimen during CCRT were factors associated with better and worse OS, respectively. In patients aged < 70 years, a PD-L1 ≥ 50% was associated with improved PFS and OS. Elderly patients experienced more treatment-related AEs, grade 3/4 AEs, permanent discontinuation of durvalumab, and treatment-related deaths. Among the AEs leading to permanent discontinuation or death, pulmonary AE was significantly more common in elderly patients., Conclusion: Durvalumab demonstrated similar outcomes in elderly compared to younger patients. However, AEs were more common in elderly patients. Thus, judicious selection of patients and chemotherapy regimens, coupled with careful AE monitoring, are important factors for ensuring optimal durvalumab treatment., Competing Interests: Disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Thyroid hormone (T3) plays a vital role in brain development and its dysregulation can impact behavior, nervous system function, and cognitive development. Large case-cohort studies have associated abnormal maternal T3 during early pregnancy to epilepsy, autism, and attention deficit hyperactivity disorder (ADHD) in children. Recent experimental findings have also shown T3's influence on the fate of neural precursor cells and raise the question of its convergence with embryonic neural progenitors. Our objective was to investigate how T3 treatment affects neuronal development and functionality at the cellular level. In vitro experiments using neural precursor cells (NPCs) measured cell growth and numbers after exposure to varying T3 concentrations. Time points included week 0 (W0) representing NPCs treated with 100 nM T3 for 5 days, and differentiated cortical neurons assessed at weeks 3 (W3), 6 (W6), and 8 (W8). Techniques such as single-cell calcium imaging and whole-cell patch clamp were utilized to evaluate neuronal activity and function. IHC staining detected mature neuron markers, and RNA sequencing enabled molecular profiling. W6 and W8 neurons exhibited higher action potential frequencies, with W6 showing increased peak amplitudes and shortened inter-spike intervals by 50%, indicating enhanced activity. Transcriptomic analysis revealed that W6 T3-treated neurons formed a distinct cluster, suggesting accelerated maturation. Comparison with the whole transcriptome further unveiled a correlation between W6 neurons treated with T3 and neuronal regulatory elements associated with autism and ADHD. These findings provide insights into T3's impact on neuronal development and potential mechanisms of T3 dysregulation and neurodevelopmental disorders., (© 2023. The Author(s).)

Protectins, 10,17-dihydroxydocosahexaenoic acids (10,17-DiHDHAs), are belonged to specialized pro-resolving mediators (SPMs). Protectins are generated by polymorphonuclear leukocytes in humans and resolve inflammation and infection in trace amounts. However, the quantitative production of protectin DX 10-epimer (10-epi-PDX, 10R,17S-4Z,7Z,11E,13Z,15E,19Z-DiHDHA) has been not attempted to date. In this study, 10-epi-PDX was quantitatively produced from docosahexaenoic acid (DHA) by serial whole-cell biotransformation of Escherichia coli expressing arachidonate (ARA) 8R-lipoxygenase (8R-LOX) from the coral Plexaura homomalla and E. coli expressing ARA 15S-LOX from the bacterium Archangium violaceum. The optimal bioconversion conditions to produce 10R-hydroxydocosahexaenoic acid (10R-HDHA) and 10-epi-PDX were pH 8.0, 30 °C, 2.0 mM DHA, and 4.0 g/L cells; and pH 8.5, 20 °C, 1.4 mM 10R-HDHA, and 1.0 g/L cells, respectively. Under these optimized conditions, 2.0 mM (657 mg/L) DHA was converted into 1.2 mM (433 mg/L) 10-epi-PDX via 1.4 mM (482 mg/L) 10R-HDHA by the serial whole-cell biotransformation within 90 min, with a molar conversion of 60% and volumetric productivity of 0.8 mM/h (288 mg/L/h). To the best of our knowledge, this is the first quantitative production of 10-epi-PDX. Our results contribute to the efficient biocatalytic synthesis of SPMs., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Lipids are key factors in regulating membrane fusion. Lipids are not only structural components to form membranes but also active catalysts for vesicle fusion and neurotransmitter release, which are driven by soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. SNARE proteins seem to be partially assembled before fusion, but the mechanisms that arrest vesicle fusion before Ca 2+ influx are still not clear. Here, we show that phosphatidylinositol 4,5-bisphosphate (PIP 2 ) electrostatically triggers vesicle fusion as an electrostatic catalyst by lowering the hydration energy and that a myristoylated alanine-rich C-kinase substrate (MARCKS), a PIP 2 -binding protein, arrests vesicle fusion in a vesicle docking state where the SNARE complex is partially assembled. Vesicle-mimicking liposomes fail to reproduce vesicle fusion arrest by masking PIP 2 , indicating that native vesicles are essential for the reconstitution of physiological vesicle fusion. PIP 2 attracts cations to repel water molecules from membranes, thus lowering the hydration energy barrier.

Background: Poor uptake to pulmonary rehabilitation (PR) is still challenging around the world. There have been few nationwide studies investigating whether PR impacts patient outcomes in COPD. We investigated the change of annual PR implementation rate, medical costs, and COPD outcomes including exacerbation rates and mortality between 2015 and 2019., Research Question: Does PR implementation improve outcomes in patients with COPD in terms of direct cost, exacerbation, and mortality?, Study Design and Methods: Data of patients with COPD extracted from a large Korean Health Insurance Review and Assessment service database (2015-2019) were analyzed to determine the trends of annual PR implementation rate and direct medical costs of PR. Comparison of COPD exacerbation rates between pre-PR and post-PR, and the time to first exacerbation and mortality rate according to PR implementation, were also assessed., Results: Among all patients with COPD in South Korea, only 1.43% received PR. However, the annual PR implementation rate gradually increased from 0.03% to 1.4% during 4 years, especially after health insurance coverage commencement. The direct medical cost was significantly higher in the PR group than the non-PR group, but the costs in these groups showed decreasing and increasing trends, respectively. Both the incidence rate and frequency of moderate-to-severe and severe exacerbations were lower during the post-PR period compared with the pre-PR period. The time to the first moderate-to-severe and severe exacerbations was longer in the PR group than the non-PR group. Finally, PR implementation was associated with a significant decrease in mortality., Interpretation: We concluded that health insurance coverage increases PR implementation rates. Moreover, PR contributes toward improving outcomes including reducing exacerbation and mortality in patients with COPD. However, despite the well-established benefits of PR, its implementation rate remains suboptimal., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

We investigated whether a homozygous recessive genetic variant of NSF attachment protein beta ( NAPB ) gene inherited by monozygotic triplets contributed to their phenotype of early-onset epilepsy and autism. Induced pluripotent stem cell (iPSC) lines were generated from all three probands and both parents. The NAPB genetic variation was corrected in iPSC lines from two probands by CRISPR/Cas9 gene editing. Cortical neurons were produced by directed, in vitro differentiation from all iPSC lines. These cell line-derived neurons enabled us to determine that the genetic variation in the probands causes exon skipping and complete absence of NAPB protein. Electrophysiological and transcriptomic comparisons of cortical neurons derived from parents and probands cell lines indicate that loss of NAPB function contributes to alterations in neuronal functions and likely contributed to the impaired neurodevelopment of the triplets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ali, Shin, Habbab, Alkhadairi, AbdelAleem, Alshaban, Park and Stanton.)

Adipose tissue invariant natural killer T (iNKT) cells are a crucial cell type for adipose tissue homeostasis in obese animals. However, heterogeneity of adipose iNKT cells and their function in adipocyte turnover are not thoroughly understood. Here, we investigate transcriptional heterogeneity in adipose iNKT cells and their hierarchy using single-cell RNA sequencing in lean and obese mice. We report that distinct subpopulations of adipose iNKT cells modulate adipose tissue homeostasis through adipocyte death and birth. We identify KLRG1 + iNKT cells as a unique iNKT cell subpopulation in adipose tissue. Adoptive transfer experiments showed that KLRG1 + iNKT cells are selectively generated within adipose tissue microenvironment and differentiate into a CX3CR1 + cytotoxic subpopulation in obese mice. In addition, CX3CR1 + iNKT cells specifically kill enlarged and inflamed adipocytes and recruit macrophages through CCL5. Furthermore, adipose iNKT17 cells have the potential to secrete AREG, and AREG is involved in stimulating adipose stem cell proliferation. Collectively, our data suggest that each adipose iNKT cell subpopulation plays key roles in the control of adipocyte turnover via interaction with adipocytes, adipose stem cells, and macrophages in adipose tissue., (© 2023. The Author(s).)

A lipoxygenase from Pleurotus sajor-caju (PsLOX) was cloned, expressed in Escherichia coli, and purified as a soluble protein with a specific activity of 629 μmol/min/mg for arachidonic acid (AA). The native PsLOX exhibited a molecular mass of 146 kDa, including a 73-kDa homodimer, as estimated by gel-filtration chromatography. The major products converted from polyunsaturated fatty acids (PUFAs), including AA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), were identified as trioxilins (TrXs), namely 13,14,15-TrXB 3 , 13,14,15-TrXB 4 , and 15,16,17-TrXB 5 , respectively, through high-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses. The enzyme displayed its maximum activity at pH 8.0 and 20 °C. Under these conditions, the specific activity and catalytic efficiency of PsLOX for PUFAs exhibited the following order: AA>EPA>DHA. Based on HPLC analysis and substrate specificity, PsLOX was identified as an arachidonate 15-LOX. PsLOX efficiently converted 10 mM of AA, EPA, and DHA to 8.7 mM of 13,14,15-TrXB 3 (conversion rate: 87 %), 7.9 mM of 13,14,15-TrXB 4 (79 %), and 7.2 mM of 15,16,17-TrXB 5 (72 %) in 15, 20, and 20 min, respectively, marking the highest conversion rates reported to date. Collectively, our results demonstrate that PsLOX is an efficient TrXs-producing enzyme., (© 2023 Wiley-VCH GmbH.)

Autism spectrum disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder linked to numerous rare, inherited, and arising de novo genetic variants. ASD often co-occurs with attention-deficit hyperactivity disorder and epilepsy, which are associated with hyperexcitability of neurons. However, the physiological and molecular mechanisms underlying hyperexcitability in ASD remain poorly understood. Transient receptor potential canonical-6 (TRPC6) is a Ca 2+ -permeable cation channel that regulates store-operated calcium entry (SOCE) and is a candidate risk gene for ASD. Using human pluripotent stem cell (hPSC)-derived cortical neurons, single-cell calcium imaging, and electrophysiological recording, we show that TRPC6 knockout (KO) reduces SOCE signaling and leads to hyperexcitability of neurons by increasing action potential frequency and network burst frequency. Our data provide evidence that reduction of SOCE by TRPC6 KO results in neuronal hyperexcitability, which we hypothesize is an important contributor to the cellular pathophysiology underlying hyperactivity in some ASD., (© 2023. The Author(s).)

Background: The Center for Personalized Precision Medicine of Tuberculosis (cPMTb) was constructed to develop personalized pharmacotherapeutic systems for tuberculosis (TB). This study aimed to introduce the cPMTb cohort and compare the distinct characteristics of patients with TB, non-tuberculosis mycobacterium (NTM) infection, or latent TB infection (LTBI). We also determined the prevalence and specific traits of polymorphisms in N-acetyltransferase-2 (NAT2) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) phenotypes using this prospective multinational cohort., Methods: Until August 2021, 964, 167, and 95 patients with TB, NTM infection, and LTBI, respectively, were included. Clinical, laboratory, and radiographic data were collected. NAT2 and SLCO1B1 phenotypes were classified by genomic DNA analysis., Results: Patients with TB were older, had lower body mass index (BMI), higher diabetes rate, and higher male proportion than patients with LTBI. Patients with NTM infection were older, had lower BMI, lower diabetes rate, higher previous TB history, and higher female proportion than patients with TB. Patients with TB had the lowest albumin levels, and the prevalence of the rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 39.2%, 48.1%, and 12.7%, respectively. The prevalence of rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 42.0%, 44.6%, and 13.3% for NTM infection, and 42.5%, 48.3%, and 9.1% for LTBI, respectively, which did not differ significantly from TB. The prevalence of the normal, intermediate, and lower transporter SLCO1B1 phenotypes in TB, NTM, and LTBI did not differ significantly; 74.9%, 22.7%, and 2.4% in TB; 72.0%, 26.1%, and 1.9% in NTM; and 80.7%, 19.3%, and 0% in LTBI, respectively., Conclusions: Understanding disease characteristics and identifying pharmacokinetic traits are fundamental steps in optimizing treatment. Further longitudinal data are required for personalized precision medicine., Trial Registration: This study registered ClinicalTrials.gov NO. NCT05280886., (© 2023. The Author(s).)

Resolvin D5 (RvD5), 7S,17S-dihydroxy-4Z,8E,10Z,13Z,15E,19Z-docosahexaenoic acid (DHA) is a specialized pro-resolving mediator (SPM) generated in human macrophages. It is implicated in the resolution of inflammation and synthesized using an inefficient chemical process. Here, DHA-enriched oil hydrolysate was prepared from oils by lipase with resin treatment and solvent extraction. The reaction factors on the biotransformation of oil hydrolysate into RvD5 were optimized using Escherichia coli expressing arachidonate double-oxygenating 15S-lipoxygenase. After optimization, the cells converted 5.0 mM (1.64 g/L) DHA in oil hydrolysate into 4.0 mM (1.44 g/L) RvD5 in a bioreactor for 3.0 h, which was 15-fold higher than that in a flask before optimization, and RvD5 with a purity of > 97% was prepared from reaction solution by treatments of resins. This is the first trial for the production of C22-dihydroxy fatty acid using a bioreactor. This study will contribute to the large-scale production of SPMs from oils., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Deok-Kun Oh reports financial support was provided by Ministry of Science and ICT, Republic of Korea. Deok-Kun Oh reports a relationship with Ministry of Science and ICT, Republic of Korea that includes: funding grants., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the effectiveness and safety of genicular artery embolization (GAE) using quick-soluble gelatin sponge particles (QS-GSPs) to alleviate chronic knee pain associated with osteoarthritis., Materials and Methods: This retrospective study included 71 patients (97 procedures, including 26 patients for both knees) who underwent GAE to treat osteoarthritic knee pain between August 2019 and January 2022. QS-GSPs were used for all the procedures. Technical success was defined as the embolization of at least 1 feeding artery. Clinical outcomes were evaluated using a 10-point visual analog scale (VAS). Clinical success was defined as a decrease in the VAS score of >50%., Results: The technical success rate was 100% (97 of 97). The mean VAS scores at baseline, immediately after TAE, and at 1 day, 1 week, 1 month, 3 months, and 6 months after TAE were 6.3, 4.3, 5.0, 3.0, 2.9, 2.9, and 2.8, respectively. The clinical success rate was 72% (70 of 97 patients) at 6 months. No major adverse events were reported, and temporary skin color change (50.5%, 49 of 97) and hematoma at the puncture site (10.3%, 10 of 97) were observed., Conclusions: GAE using QS-GSPs had a high technical success rate and was considered safe. Clinical outcomes using QS-GSPs were comparable with those of existing materials., (Copyright © 2023 SIR. Published by Elsevier Inc. All rights reserved.)

The analysis of otolith Sr isotope ratios ( 87 Sr/ 86 Sr) is a powerful method to study fish migration in freshwater areas. However, few studies have applied this method to study fish movement in brackish-water environments. Furthermore, despite the fact that habitat differentiation has been shown to drive genetic differentiation and reproductive isolation among stickleback fish, no studies have used the otolith 87 Sr/ 86 Sr ratios to analyze habitat differentiation between stickleback ecotypes and species. In this study, we analyzed the otolith 87 Sr/ 86 Sr ratios of three sympatric stickleback species of the genus Pungitius in the Shiomi River on Hokkaido Island, Japan: P. tymensis , the brackish-water type of the P. pungitius-P. sinensis complex, and the freshwater type of the P. pungitius-P. sinensis complex. First, we created a mixing equation to depict the relationship between habitat salinity and the 87 Sr/ 86 Sr ratios of river water. We found that the otolith 87 Sr/ 86 Sr ratios differed significantly among the three species, indicating that the three species utilize habitats with different salinities: P. tymensis and the brackish-water type inhabit freshwater and brackish-water environments, respectively, with the freshwater type using intermediate habitats. In addition, we found that some freshwater individuals moved to habitats with higher salinities as they grew. Our study demonstrates that the analysis of otolith 87 Sr/ 86 Sr ratios is a useful method for studying the habitat use of fish in brackish-water environments and habitat differentiation among closely related sympatric and parapatric species., Competing Interests: We have no conflicts of interest associated with this publication., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Long-acting β 2 -agonist (LABA)/long-acting muscarinic-antagonist (LAMA) dual therapy has been found to be more effective than LAMA monotherapy in the treatment of chronic obstructive pulmonary disease (COPD). However, among patients with group B or D COPD, the characteristics of patients for whom LABA/LAMA dual therapy is superior to LAMA monotherapy in minimizing acute exacerbations remain unknown. With data from a prospective COPD cohort, subgroup analyses were conducted to determine whether LABA/LAMA dual therapy was superior to LAMA monotherapy in reducing the rate of acute exacerbations in group B and D COPD patients. Group B and D COPD patients taking LAMA or LABA/LAMA were enrolled according to the 2022 Global initiative for Chronic Obstructive Pulmonary Disease guidelines. A total of 737 patients were included in this study: 600 with group B COPD and 137 with group D COPD. Compared with patients taking LAMA monotherapy, those taking LABA/LAMA had a significantly lower incidence of acute exacerbations over 1 year. In the subgroup of patients ≥70 years old, there was a significantly lower risk of severe COPD exacerbations among group B patients taking LABA/LAMA than among those taking LAMA monotherapy (odds ratio [OR], 0.258; 95% confidence interval [CI], 0.095-0.703). In contrast, in the subgroup of group D patients with COPD Assessment Test scores ≥25, compared with LAMA monotherapy, LABA/LAMA treatment was associated with lower risk of severe COPD exacerbations (OR, 0.115; 95% CI, 0.018-0.749). The combination of LABA and LAMA was found to be superior to LAMA monotherapy, especially for treating older adults with group B COPD, as well as for group D patients with severe symptoms., Competing Interests: CONFLICT OF INTEREST STATEMENT: None declared., (© Chonnam Medical Journal, 2023.)

Compound K (C-K), one of the most bioactive ginsenoside, is produced by hydrolyzing the glycoside moieties of protopanaxadiol (PPD)-type glycosylated ginsenosides in the ginseng extract. To enhance the biotransformation of PPD-type ginsenosides in American ginseng extract (AGE) into C-K, the optimization of the feed type, concentration, and period for the carbon source sucrose and the reactant AGE was performed in fed-batch fermentation of Aspergillus tubingensis using a fermenter. The concentration (3.94 g/L) and productivity (27.4 mg/L/h) of C-K after feed optimization in fed-batch fermentation increased 3.1-fold compared to those (1.29 g/L and 8.96 mg/L/h) in batch fermentation, and a molar conversion of 100% was achieved. To the best of our knowledge, this is the first trial of fed-batch fermentation to convert ginseng extract into deglycosylated ginsenoside and the highest reported C-K concentration and productivity using ginseng extract via fermentation. After ethanol and resin treatments, C-K solids with purities of 59% and 96% were obtained from the fermentation broth as food- and pharmaceutical-grade products, respectively., (© 2023. The Author(s).)

Objective: Impaired lung function is associated with an increased risk for cognitive decline. F-18 fluorodeoxyglucose (FDG) PET is a well-known neurodegenerative biomarker for dementia. We investigated the association between lung and brain function using FDG PET in patients with lung cancer., Methods: A random sub-sample of 102 patients with lung cancer and without a self-reported history of neuropsychiatric disorders were recruited and underwent both lung function tests and FDG PET scans before treatment. Lung function was analyzed as the percentage predicted value (% pred) of forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1). FDG uptake was measured as standardized uptake values (SUVs) in the frontal, parietal, temporal, and occipital cortices and cognition-related regions. Regional SUV ratios (SUVRs) were calculated by dividing the SUV in each region by the whole-brain SUV and were then evaluated against lung function indices and clinical variables., Results: After excluding five patients with brain metastases, 97 patients were included in the final analysis (mean age, 67.7 ± 10.3 years). Mean FVC and mean FEV1 were 80.0% ± 15.4% and 77.6% ± 17.8%, respectively. Both FVC and FEV1 were positively correlated with SUVRs in all brain regions after adjusting the data for clinical variables. The degree of decrease in SUVRs related to lung function was not significantly different between cognition-related regions and other regions., Conclusion: Impaired lung function was associated with decreased glucose metabolism in all regions of the brain, indicating that cognitive decline related to decreased glucose metabolism may be due to reduced perfusion., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The graft survival rate of full-thickness corneal xenotransplantation (XTP) with minimal immunosuppression in genetically engineered pigs is unknown, whereas lamellar corneal XTP shows satisfactory results. We compared graft survival between full-thickness and lamellar transplantations in the same genetically engineered pig., Methods: Six pig-to-monkey corneal transplantations were performed on 3 transgenic pigs. Two corneas harvested from 1 pig were transplanted into 2 monkeys using full-thickness and lamellar corneal xenotransplantation. The transgenic donor pigs used were α1,3-galactosyltransferase gene-knockout + membrane cofactor protein (GTKO+CD46) in one recipient and GTKO+CD46+ thrombomodulin (TBM) in the other., Results: The graft survival time for GTKO+CD46 XTP was 28 days. With the addition of TBM, the survival differences between lamellar and full-thickness XTP were 98 days versus 14 days and >463 days (ongoing) versus 21 days, respectively. An excessive number of inflammatory cells was observed in failed grafts, but none were in the recipient's stromal bed., Conclusions: Unlike full-thickness corneal XTP, lamellar xenocorneal transplantation does not exhibit surgical complications, such as retrocorneal membrane or anterior synechia. The graft survival of lamellar XTP in this study was not as good as in our previous experiments, although the survival period was superior to that of full-thickness XTP. The difference in graft survival based on transgenic type is not definitive. Further studies using transgenic pigs and minimal immunosuppression need to focus on improving graft survival of lamellar XTP and using a larger sample size to determine the potential of full-thickness corneal XTP., (Copyright © 2023. Published by Elsevier Inc.)

Background: In South Korea, pig-to-nonhuman primate trials of solid organs have only been performed recently, and the results are not sufficiently satisfactory to initiate clinical trials. Since November 2011, we have performed 30 kidney pig-to-nonhuman primate xenotransplantations at Konkuk University Hospital., Methods: Donor αGal-knockout-based transgenic pigs were obtained from 3 institutes. The knock-in genes were CD39, CD46, CD55, CD73, and thrombomodulin, and 2-4 transgenic modifications with GTKO were done. The recipient animal was the cynomolgus monkey. We used the immunosuppressants anti-CD154, rituximab, anti-thymocyte globulin, tacrolimus, mycophenolate mofetil, and steroids., Results: The mean survival duration of the recipients was 39 days. Except for a few cases for which survival durations were <2 days because of technical failure, 24 grafts survived for >7 days, with an average survival duration of 50 days. Long-term survival was observed 115 days after the removal of the contralateral kidney, which is currently the longest-recorded graft survival in Korea. We confirmed functioning grafts for the surviving transplanted kidneys after the second-look operation, and no signs of hyperacute rejection were observed., Conclusions: Although our survival results are relatively poor, they are the best-recorded results in South Korea, and the ongoing results are improving. With the support of government funds and the volunteering activities of clinical experts, we aim to further improve our experiments and contribute to the commencement of clinical trials of kidney xenotransplantation in Korea., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cholesterol is essential for neuronal activity and function. Cholesterol depletion in the plasma membrane impairs synaptic transmission. However, the molecular mechanisms by which cholesterol deficiency leads to defects in vesicle fusion remain poorly understood. Here, it is shown that cholesterol is required for Ca 2+ -dependent native vesicle fusion using the in vitro reconstitution of fusion and amperometry to monitor exocytosis in chromaffin cells. Purified native vesicles are crucial for the reconstitution of physiological Ca 2+ -dependent fusion, because vesicle-mimicking liposomes fail to reproduce the cholesterol effect. Intriguingly, cholesterol has no effect on the membrane binding of synaptotagmin-1, a Ca 2+ sensor for ultrafast fusion. Cholesterol strengthens local membrane deformation and bending induced by synaptotagmin-1, thereby lowering the energy barrier for Ca 2+ -dependent fusion to occur. The data provide evidence that cholesterol depletion abolishes Ca 2+ -dependent vesicle fusion by disrupting synaptotagmin-1-induced membrane bending, and suggests that cholesterol is an essential lipid regulator for Ca 2+ -dependent fusion., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The SARS-CoV-2 coronavirus, which causes a respiratory disease called COVID-19, has been declared a pandemic by the World Health Organization (WHO) and is still ongoing. Vaccination is the most important strategy to end the pandemic. Several vaccines have been approved, as evidenced by the ongoing global pandemic, but the pandemic is far from over and no fully effective vaccine is yet available. One of the most critical steps in vaccine development is the selection of appropriate antigens and their proper introduction into the immune system. Therefore, in this study, we developed and evaluated two proposed vaccines composed of single and multiple SARS-CoV-2 polypeptides derived from the spike protein, namely, vaccine A and vaccine B, respectively. The polypeptides were validated by the sera of COVID-19-vaccinated individuals and/or naturally infected COVID-19 patients to shortlist the starting pool of antigens followed by in vivo vaccination to hACE2 transgenic mice. The spike multiple polypeptide vaccine (vaccine B) was more potent to reduce the pathogenesis of organs, resulting in higher protection against the SARS-CoV-2 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hisham, Seo, Kim, Shim, Hwang, Yoo, Kim, Song, Jhun, Park, Lee, Shin, Han, Seong, Choi and Kim.)

A recombinant putative lipoxygenase (LOX) from Danio rerio (zebrafish), ALOX3c protein with 6-histidine tag, was purified using affinity chromatography, with a specific activity of 17.2 U mg -1 for arachidonic acid (AA). The molecular mass of the native ALOX3c was 156 kDa composed of a 78-kDa dimer by gel-filtration chromatography. The product obtained from the conversion of AA was identified as 5S-hydroxyeicosatetraenoic acid (5S-HETE) by HPLC and LC-MS/MS analyses. The specific activity and catalytic efficiency of the LOX from D. rerio for polyunsaturated fatty acids (PUFAs) followed the order AA (17.2 U mg -1 , 1.96 s -1  μM -1 ) > docosahexaenoic acid (DHA, 13.6 U mg -1 , 0.91 s -1  μM -1 ) > eicosapentaenoic acid (EPA, 10.5 U mg -1 , 0.65 s -1  μM -1 ) and these values for AA were the highest among the 5S-LOXs reported to date. Based on identified products and substrate specificity, the enzyme is an AA 5S-LOX. The enzyme exhibited the maximal activity at pH 8.0 and 20 °C with 0.1 mM Zn 2+ in the presence of 10 mM cysteine. Under these reaction conditions, 6.88 U mL -1 D. rerio 5S-LOX converted 1.0 mM of AA, EPA, and DHA to 0.91 mM 5S-HETE, 0.72 mM 5S-hydroxyeicosapentaenoic acid (5S-HEPE), and 0.68 mM 7S-hydroxydocosahexaenoic acid (7S-HDHA) in 25, 30, and 25 min, corresponding to molar conversion rates of 91, 72, and 68% and productivities of 2.18, 1.44, and 1.63 mM h -1 , respectively. To the best of our knowledge, this study is the first to describe the bioconversion into 5S-HETE, 5S-HEPE, and 7S-HDHA for the application of biotechnological production., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Platycosides, saponins from balloon flower root (Platycodi radix), have diverse health benefits, such as antioxidant, anti-inflammatory, anti-tussive, anti-cancer, anti-obesity, anti-diabetes, and whitening activities. Deglycosylated platycosides, which show greater biological effects than glycosylated platycosides, are produced by the hydrolysis of glycoside moieties in glycosylated platycosides. In this review, platycosides are classified according to the chemical structures of the aglycone sapogenins and also divided into natural platycosides, including major, minor, and rare platycosides, depending on the content in Platycodi radix extract and biotransformed platycosides. The biological activities of platycosides are summarized and methods for deglycosylation of saponins, including physical, chemical, and biological methods, are introduced. The biotransformation of glycosylated platycosides into deglycosylated platycosides was described based on the hydrolytic pathways of glycosides, substrate specificity of glycosidases, and specific productivities of deglycosylated platycosides. Methods for producing diverse and/or new deglycosylated platycosides are also proposed.

The putative lipoxygenase (LOX) from the proteobacterium Shewanella hanedai was determined to be an 82 kDa monomeric enzyme by SDS-PAGE and gel filtration chromatography analysis. LOX was identified as a single-dioxygenating arachidonate (ARA) 9S-LOX by analyzing ARA-derived bioconversion products using high-performance liquid chromatography with reverse-, normal-, and chiral-phase columns and evaluating kinetic parameters for C20- and C22-polyunsaturated fatty acids (PUFAs). The catalytic efficiency (k cat /K m ) values of 9S-LOX from S. hanedai for ARA, eicosapentaenoic acid, and docosahexaenoic acid were 3.1-, 4.1-, and 2.5-fold higher, respectively, than those only reported 9S-LOX from Sphingopyxis macrogoltabida with double-dioxygenating activity. To promote the production of C20 9S- and C22 11S-hydroxy fatty acids (HFAs) using Escherichia coli expressing 9S-LOX from S. hanedai, bioconversion conditions, including temperature, pH, solvent type and its concentration, concentrations of cells, and substrate, were optimized to 25 °C, pH 8.5, 6% (v/v) dimethyl sulfoxide, 0.2 g/l cells, and 7 mM ARA as substrate in a 500 ml-Erlenmeyer baffled flask with 50 ml reaction solution with agitation at 200 rpm in the presence of 10 mM cysteine as a reduction agent, respectively. Under these conditions, 6.4 mM 9S-hydroxyeicosatetraenoic acid, 6.2 mM 9S-hydroxyeicosapentaenoic acid, and 5.9 mM 11S-hydroxydocosahexaenoic acid were produced in 30 min, 40 min, and 60 min with specific productivities of 1067 μmol/min/g, 775 μmol/min/g, and 492 μmol/min/g, volumetric productivities of 213 μM/min, 155 μM/min, and 98 μM/min, and conversion yields of 91.4%, 88.6%, and 84.3%, respectively. To date, these are the highest specific productivities reported for the bioconversion of C20- and C22-PUFAs into HFAs. KEY POINTS: • Lipoxygenase from Shewanella hanedai was identified as arachidonate 9S-lipoxygenase • Optimization led to increased production of C20 9S- and C22 11S-hydroxy fatty acids • We reported the highest specific productivities of C20- and C22-hydroxy fatty acids., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In mammals, brown adipose tissue (BAT) is specialized to conduct non-shivering thermogenesis for survival under cold acclimation. Although emerging evidence suggests that lipid metabolites are essential for heat generation in cold-activated BAT, the underlying mechanisms of lipid uptake in BAT have not been thoroughly understood. Here, we show that very-low-density lipoprotein (VLDL) uptaken by VLDL receptor (VLDLR) plays important roles in thermogenic execution in BAT. Compared with wild-type mice, VLDLR knockout mice exhibit impaired thermogenic features. Mechanistically, VLDLR-mediated VLDL uptake provides energy sources for mitochondrial oxidation via lysosomal processing, subsequently enhancing thermogenic activity in brown adipocytes. Moreover, the VLDL-VLDLR axis potentiates peroxisome proliferator activated receptor (PPAR)β/δ activity with thermogenic gene expression in BAT. Accordingly, VLDL-induced thermogenic capacity is attenuated in brown-adipocyte-specific PPARβ/δ knockout mice. Collectively, these data suggest that the VLDL-VLDLR axis in brown adipocytes is a key factor for thermogenic execution during cold exposure., Competing Interests: Declaration of interests The authors declare no competing financial interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for chronic obstructive pulmonary disease (COPD) recommend considering patient preference when choosing an inhaler device. However, few studies have assessed both inhaler satisfaction and factors associated with high inhaler satisfaction. Therefore, we assessed inhaler satisfaction and determinants of high satisfaction in Korean COPD patients., Methods: COPD patients were prospectively enrolled from January 2018 to November 2019. The 308 inhalers used by the 261 participants in this study included dry powder inhalers (Turbuhaler, Breezhaler, Ellipta, Diskus, and Genuair), a soft mist inhaler (Respimat), and pressurized metered dose inhalers (pMDIs). Inhaler satisfaction was assessed by the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire. High inhaler satisfaction was defined as an FSI-10 ≥ 43., Results: Among 261 COPD patients, 163 (62.5%) were highly satisfied with their inhaler device. The rates of high inhaler satisfaction for Turbuhaler, Breezhaler, Ellipta, Diskus, Genuair, Respimat, and pMDI usage were 40.0%, 67.2%, 66.7%, 50.0%, 55.6%, 63.4%, and 45.0%, respectively ( P = 0.215). In univariate analyses, higher body mass index, non-current smoker, GOLD grades I and II, a modified Medical Research Council (mMRC) score < 2, lower inhaler puff burden, once daily usage of inhaler, and good inhaler adherence were associated with high inhaler satisfaction. In multivariate analyses, an mMRC score < 2, and good inhaler adherence were independently associated with high inhaler satisfaction., Conclusion: High inhaler satisfaction was associated with dyspnea symptom and good inhaler adherence in COPD patients. Effective strategies are needed including appropriate inhaler device selection, consideration of patient preference, and repeated inhaler education to improve patient satisfaction of inhalers., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Background: Tuberculosis (TB) is a highly heterogeneous disease that can affect any organ. Extrapulmonary TB (EPTB) is more difficult to diagnose due to various clinical presentations. Depending on the characteristics of the patient, the involved site of TB may vary. However, data on clinical characteristics of EPTB are inconsistent and insufficient. This study aimed to identify the characteristics of patients with pulmonary TB (PTB) and EPTB and describe characteristic differences for each involved site., Methods: We systemically collected data of TB patients included in the national surveillance system in South Korea from July 2018 to June 2019 and compared the characteristics of patients with EPTB with that of PTB., Results: A total of 7674 patients with a mean age of 60.9 years were included. Among them, 6038 (78.7%) patients were diagnosed with PTB and 1636 (21.3%) with EPTB. In PTB group, the mean age (61.7 ± 18.7 vs. 57.8 ± 19.9) and proportion of male sex (63.3% vs. 50.1%) were higher, but the body mass index was lower (21.2 ± 3.4 vs. 22.7 ± 3.5) than that of the EPTB group. Prevalence of diabetes (20.5% vs. 16.9%) and chronic lung disease (5.1% vs. 2.9%) were higher in PTB group, meanwhile, those of chronic kidney disease (CKD) (2.7% vs. 5.4%) and long-term steroid use (0.4% vs. 1.0%) were higher in EPTB group. Abdominal TB was more prevalent in patients with chronic liver disease (odds ratio [OR]: 2.69, 95% CI: 1.52-4.74), and urogenital TB was more prevalent in patients with CKD (OR: 2.75, 95% CI: 1.08-6.99)., Conclusions: We found that underlying comorbidities were closely associated with the location of TB development, and therefore, the possibility of EPTB should be carefully evaluated while monitoring for underlying disease in TB-endemic areas., (© 2022. The Author(s).)

Genome-wide chromosomal microarray is extensively used to detect copy number variations (CNVs), which can diagnose microdeletion and microduplication syndromes. These small unbalanced chromosomal structural rearrangements ranging from 1 kb to 10 Mb comprise up to 15% of human mutations leading to monogenic or contiguous genomic disorders. Albeit rare, CNVs at 1p13.3 cause a variety of neurodevelopmental disorders (NDDs) including development delay (DD), intellectual disability (ID), autism, epilepsy, and craniofacial anomalies (CFA). Most of the 1p13.3 CNV cases reported in the pre-microarray era encompassed a large number of genes and lacked the demarcating genomic coordinates, hampering the discovery of positional candidate genes within the boundaries. In this study, we present four subjects with 1p13.3 microdeletions displaying DD, ID, autism, epilepsy, and CFA. In silico comparative genomic mapping with three previously reported subjects with CNVs and 22 unreported DECIPHER CNV cases has resulted in the identification of four different sub-genomic loci harboring five positional candidate genes for DD, ID, and CFA at 1p13.3. Most of these genes have pathogenic variants reported, and their interacting genes are involved in NDDs. RT-qPCR in various human tissues revealed a high expression pattern in the brain and fetal brain, supporting their functional roles in NDDs. Interrogation of variant databases and interacting protein partners led to the identification of another set of 11 potential candidate genes, which might have been dysregulated by the position effect of these CNVs at 1p13.3. Our studies define 1p13.3 as a genomic region harboring 16 NDD candidate genes and underscore the critical roles of small CNVs in in silico comparative genomic mapping for disease gene discovery. Our candidate genes will help accelerate the isolation of pathogenic heterozygous variants from exome/genome sequencing (ES/GS) databases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ben-Mahmoud, Jun, Gupta, Shastri, de la Fuente, Park, Shin, Kim, da Cruz, Pinto, Minasi, Silva da Cruz, Faivre, Callier, Racine, Layman, Kong, Kim, Kim and Kim.)

Water scarcity is a serious agricultural problem causing significant losses to crop yield and product quality. The development of technologies to mitigate the damage caused by drought stress is essential for ensuring a sustainable food supply for the increasing global population. We herein report that the exogenous application of ethanol, an inexpensive and environmentally friendly chemical, significantly enhances drought tolerance in Arabidopsis thaliana, rice and wheat. The transcriptomic analyses of ethanol-treated plants revealed the upregulation of genes related to sucrose and starch metabolism, phenylpropanoids and glucosinolate biosynthesis, while metabolomic analysis showed an increased accumulation of sugars, glucosinolates and drought-tolerance-related amino acids. The phenotyping analysis indicated that drought-induced water loss was delayed in the ethanol-treated plants. Furthermore, ethanol treatment induced stomatal closure, resulting in decreased transpiration rate and increased leaf water contents under drought stress conditions. The ethanol treatment did not enhance drought tolerance in the mutant of ABI1, a negative regulator of abscisic acid (ABA) signaling in Arabidopsis, indicating that ABA signaling contributes to ethanol-mediated drought tolerance. The nuclear magnetic resonance analysis using 13C-labeled ethanol indicated that gluconeogenesis is involved in the accumulation of sugars. The ethanol treatment did not enhance the drought tolerance in the aldehyde dehydrogenase (aldh) triple mutant (aldh2b4/aldh2b7/aldh2c4). These results show that ABA signaling and acetic acid biosynthesis are involved in ethanol-mediated drought tolerance and that chemical priming through ethanol application regulates sugar accumulation and gluconeogenesis, leading to enhanced drought tolerance and sustained plant growth. These findings highlight a new survival strategy for increasing crop production under water-limited conditions., (© The Author(s) 2022. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.)

Purpose: Peroxidation and reduction of 11S- and 13S-positions on C20 and C22 polyunsaturated fatty acids (PUFAs) by Escherichia coli expressing highly active arachidonate (ARA) 11S-lipoxygenase (11S-LOX) from Enhygromyxa salina with the reducing agent cysteine., Results: The specific activity and catalytic efficiency of ARA 11S-LOX from E. salina were 4.1- and 91-fold higher than those of only reported ARA 11S-LOX from Myxococcus xanthus, respectively. The hydroxy fatty acids (HFAs) obtained by the biotransformation of ARA, eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexanoic acid (DHA) by Escherichia coli expressing 11S-LOX from E. salina in the presence of cysteine were identified as 11S-hydroxyeicosatetraenoic acid (11S-HETE), 11S-hydroxyeicosapentaenoic acid (11S-HEPE), 13S-hydroxydocosapentaenoic acid (13S-HDPA), and 13S-hydroxydocosahexaenoic acid (13S-HDHA), respectively. The recombinant cells converted 3 mM of ARA, EPA, DPA, and DHA into 2.9 mM of 11S-HETE, 2.4 mM 11S-HEPE, 1. 9 mM 13S-HDPA, and 2.2 mM 13S-HDHA in 60, 80, 120, and 120 min, corresponding to productivities of 72.5, 40.4, 18.5, and 22.4 μM min -1 and conversion yields of 96.7, 80.0, 62.3, and 74.6%, respectively., Conclusions: We report the highest concentrations, conversion yields, and productivities of 11S- and 13S-hydroxy fatty acids from C20- and C22-PUFAs achieved via E. coli expressing highly active E. salina 11S-LOX., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)