Microbial upcycling of methane to phytoene using metabolically engineered Methylocystis sp. MJC1 strain.

Methane, a potent greenhouse gas, requires sustainable mitigation strategies. Here, the microbial upcycling of methane to phytoene, a valuable colorless carotenoid with applications in the cosmeceutical industry was demonstrated. To achieve this goal, a stepwise metabolic engineering approach was employed in Methylocystis sp. MJC1, a methane-oxidizing bacterium. The incorporation of crtE and crtB genes from Deinococcus radiodurans R1 established the phytoene biosynthetic pathway. This pathway was fine-tuned through promoter optimization, resulting in a phytoene production of 450 µg/L from 37 mmol/L methane. Disrupting the ackA gene reduced a by-product, acetate, by 50 % and increased phytoene production by 56 %. Furthermore, overexpressing the dxs gene boosted phytoene titer 3-fold. The optimized strain produced 15 mg/L phytoene from 2 mol/L methane in fed-batch fermentation, a 4-fold increase in phytoene titer and 4-fold in yield. This demonstrates Methylocystis sp. MJC1's potential for efficient phytoene production and presents a novel approach for greenhouse gas reduction.

Multi-Objective Bayesian Optimization for Laminate-Inspired Mechanically Reinforced Piezoelectric Self-Powered Sensing Yarns.

Piezoelectric fiber yarns produced by electrospinning offer a versatile platform for intelligent devices, demonstrating mechanical durability and the ability to convert mechanical strain into electric signals. While conventional methods involve twisting a single poly(vinylidene fluoride-co-trifluoroethylene)(P(VDF-TrFE)) fiber mat to create yarns, by limiting control over the mechanical properties, an approach inspired by composite laminate design principles is proposed for strengthening. By stacking multiple electrospun mats in various sequences and twisting them into yarns, the mechanical properties of P(VDF-TrFE) yarn structures are efficiently optimized. By leveraging a multi-objective Bayesian optimization-based machine learning algorithm without imposing specific stacking restrictions, an optimal stacking sequence is determined that simultaneously enhances the ultimate tensile strength (UTS) and failure strain by considering the orientation angles of each aligned fiber mat as discrete design variables. The conditions on the Pareto front that achieve a balanced improvement in both the UTS and failure strain are identified. Additionally, applying corona poling induces extra dipole polarization in the yarn state, successfully fabricating mechanically robust and high-performance piezoelectric P(VDF-TrFE) yarns. Ultimately, the mechanically strengthened piezoelectric yarns demonstrate superior capabilities in self-powered sensing applications, particularly in challenging environments and sports scenarios, substantiating their potential for real-time signal detection.

Circular economy approach: Nutrient recovery and economical struvite production from wastewater sources by using modified biochars.

The enrichment of phosphorus (P) and nitrogen (N) in aquatic systems can cause eutrophication. Moreover, P rocks may become exhausted in the next 100 years. A slow-release fertilizer called struvite (MgNH4PO4.6H2O) can reduce surface runoff. However, the high cost of raw material or chemicals is a bottleneck in their economical production. Therefore, incinerated sewage sludge ash, food wastewater, and bittern were combined as the sources of P, N, and Mg, respectively. Sawdust biochar was used to enhance the adsorptive recovery of nutrients. First, recovery kinetics was studied by comparing bittern-impregnated biochar (BtB) with the Mg-impregnated biochar (MgB). Subsequently, the synergistic physical and chemical interactions were observed for P and N recovery. Almost complete PO43-P recoveries were achieved within 10 min for both biochars. However, NH4+-N recovery was stable after 2 h, with 26% recovery by MgB and 20% recovery by BtB. Biochars activated with steam (steam-activated biochar) and KOH (KOH-activated biochar) gave superior activities to those of unactivated biochars and activated carbon (AC) nutrient recovery and struvite purity. Moreover, the activated biochars showed a lower risk of surface runoff, similar to that of AC. Therefore, activated biochars can be used as an alternative to AC for economical struvite production from a combination of wastewater sources.

Cancer treatment-induced bone loss.

Cancer treatment-induced bone loss (CTBL) is associated with anti-tumor treatments, including endocrine therapies, chemotherapeutic treatments, radiotherapy, glucocorticoids, and tyrosine kinase inhibitors. Osteoporosis, characterized by the loss of bone mass, can increase the risk of fractures, leading to mortality and long-term disability, even after cancer remission. Cancer and osteoporosis have marked clinical and pathogenetic similarities. Both have a multifactorial etiology, affect the geriatric population, and markedly influence quality of life. Lifestyle management, including calcium and vitamin D supplementation, is recommended but the supporting evidence is limited. Oral and injectable bisphosphonates are effective for osteoporosis and malignant bone disease. Bisphosphonates increase bone mineral density (BMD) in patients with CTBL. Denosumab is also used in the management of CTBL; in clinical trials, it improved BMD and reduced the risk of fracture. Currently, there are no bone anabolic therapies for patients with cancer. Appropriate therapies are necessary to maintain optimal bone health, particularly in patients at heightened risk.

Changes in nonalcoholic fatty liver disease and M2BPGi due to lifestyle intervention in primary healthcare.

BACKGROUND: A healthy lifestyle is the most important method for managing nonalcoholic fatty liver disease (NAFLD). Mac-2-binding protein glycosylated isomer (M2BPGi) has been suggested as a biomarker for NAFLD. This study aimed to determine the efficacy of personalized lifestyle interventions on NAFLD remission. METHODS: This single-arm intervention study recruited participants with NAFLD who underwent health checkups at seven health-promotion centers in five South Korean cities. Fatty liver diagnosis was based on ultrasonography (US). The 109 individuals were recruited for personalized lifestyle interventions of hypocaloric diets and exercise. The participants attended the lifestyle intervention programs once per month for the first 3 months, and once every 3 months for the subsequent 6 months. In addition to sessions through center visits, phone-based intervention and self-monitoring at 4-, 5-, 7-, and 8-month were provided during the 9-month intervention period. And phone-based self-monitoring were also provided monthly during the 3-month follow-up period. The primary outcome was NAFLD remission at month 12 as measured on US and magnetic resonance elastography. The secondary outcomes were the changes in metabolic factors and M2BPGi. RESULTS: The 108 individuals (62 males and 46 females; age 51.1±12.4 years, mean±standard deviation) were finally analyzed after the 12month intervention. Body mass index, waist circumference (WC), blood pressure, blood lipids (total cholesterol, triglycerides, and HDL-C), and fasting blood sugar levels were improved relative to baseline (all P<0.05). Fatty liver at or above the moderate grade according to US was decreased at month 12 relative to baseline (67.6% vs 50.9%) (P = 0.002). M2BPGi levels decreased during the 12-month study period (P<0.001). M2BPGi levels were moderately correlated with hepatic fat fraction by magnetic resonance imaging (r = 0.33, P = 0.05). WC (OR = 0.82, 95% CI = 0.67-1.00, P = 0.05) and HDL-C (OR = 1.17, 95% CI = 1.03-1.32, P = 0.014) were associated with remission of fatty liver in the multivariate analysis. CONCLUSION: The personalized lifestyle intervention was effective in improving fatty liver and metabolic factors, but not hepatic stiffness, in NAFLD. TRIAL REGISTRATION: ICTRP, cris.nih.go.kr (KCT0006380).

Impact of Nontreatment Duration and Keratopathy on Major Adverse Cardiovascular Events in Fabry Disease: A Nationwide Cohort Study.

Fabry disease (FD) is a rare inherited X-linked lysosomal storage disorder that results in the progressive accumulation of glycosphingolipids in multiple organs. Early FD-specific treatments may improve clinical outcomes; however, clinical evidence about early FD treatment is limited. We aimed to determine the cardiovascular outcomes of patients with FD who received enzyme replacement therapy. This nationwide observational study was conducted using the National Health Claims database of the Korean population with FD. The primary outcome was major adverse cardiovascular events (MACEs). MACE risk factors in FD were evaluated using time-dependent Cox regression. Between January 2007 and April 2022, 188 patients with FD were analyzed. Among them, 22 (11.7%) experienced MACE (males: 14/95 [14.7%]; females: 8/93 [8.6%]). The mean age at MACE diagnosis was 53.5 ± 11.0 years in all patients with FD, which was lower in males compared with in females (49.7 ± 9.6 vs. 60.0 ± 10.7 years, p = 0.030). Multivariate analysis (HR, 95% CI) revealed that age (1.042; 1.004-1.082) and duration of FD nontreatment (1.040; 1.003-1.078) were significant MACE risk factors in all patients. In males, age (1.080; 1.032-1.131), FD nontreatment duration (1.099; 1.048-1.152), and keratopathy (18.920; 4.174-85.749) were significant MACE risk factors in multivariate analysis. In females, the only significant MACE risk factor was a high Charlson comorbidity index score (1.795; 1.229-2.622). In conclusion, duration of FD nontreatment and keratopathy are significant MACE risk factors in males with FD. These findings suggest the importance of early initiation of FD-specific treatment and careful evaluation of keratopathy in males with FD.

Physical Unclonable Functions Employing Circularly Polarized Light Emission from Nematic Liquid Crystal Ordering Directed by Helical Nanofilaments.

This study proposes the use of physical unclonable functions employing circularly polarized light emission (CPLE) from nematic liquid crystal (NLC) ordering directed by helical nanofilaments in a mixed system composed of a calamitic NLC mixture and a bent-core molecule. To achieve this, an intrinsically nonemissive NLC is blended with a high concentration of a luminescent rod-like dye, which is miscible up to 10 wt % in the calamitic NLC without a significant decrease in the degree of alignment. The luminescence dissymmetry factor of CPLEs in the mixed system strongly depends on the degree of alignment of the dye-doped NLCs. Furthermore, the mixed system prepared in this study exhibits two randomly generated chiral domains with CPLEs of opposite signs. These chiral domains are characterized not only by their CPLE performances but also by their ability to generate random patterns up to several millimeters, making them promising candidates for high-performance secure authentication applications.

Enhanced mono-aromatics production by the CH4-assisted pyrolysis of microalgae using Zn-based HZSM-5 catalysts.

This study presents the catalytic pyrolysis of microalgae, Chlorella vulgaris (C. vulgaris), using pure CH4 and H2-rich gas evolved from CH4 decomposition on three different HZSM-5 catalysts loaded with Zn, Ga, and Pt, aimed specifically at producing high-value mono-aromatics such as benzene, toluene, ethylbenzene, and xylene (BTEX). In comparison with that for the typical inert N2 environment, a pure CH4 environment increased the bio-oil yield from 32.4 wt% to 37.4 wt% probably due to hydrogen and methyl radical insertion in the bio-oil components. Furthermore, the addition of bimetals further increased bio-oil yield. For example, ZnPtHZ led to a bio-oil yield of 47.7 wt% in pure CH4. ZnGaHZ resulted in the maximum BTEX yield (6.68 wt%), which could be explained by CH4 activation, co-aromatization, and hydrodeoxygenation. The BTEX yield could be further increased to 7.62 wt% when pyrolysis was conducted in H2-rich gas evolved from CH4 decomposition over ZnGaHZ, as rates of aromatization and hydrodeoxygenation were relatively high under this condition. This study experimentally validated that the combination of ZnGaHZ and CH4 decomposition synergistically increases BTEX production using C. vulgaris.

Reference intervals of cell population data parameters in Sysmex XN-Series and its patterns of changes from early adulthood to geriatric ages in South Korea.

INTRODUCTION: Cell population data (CPD) parameters may be putative biomarkers for the screening of various diseases including some infections and myelodysplastic syndrome. This study aimed to establish the age- and sex-specific reference intervals (RIs) for the CPD parameters in the Korean population. METHODS: The reference population for the RIs of CPD parameters comprised 124 856 subjects aged 20-99 years. CPD parameters were obtained from Sysmex XN-2000 (Kobe, Japan) datasets from 17 health promotion centers in 13 South Korean cities. We determined significant partitions for age and sex, and calculated RIs according to Clinical and Laboratory Standards Institute C28-A3 guidelines. RESULTS: The side scattered light intensity in the neutrophil area and the lymphocyte area did not require sex-related partitioning except in those over the age of 50, among whom the lower limit (LL) and upper limit (UL) were lower in females. However, the side scattered light distribution width in the lymphocyte area required age- and sex-related partitioning, in which LL and UL were higher in females. The LL and UL of the fluorescent light distribution width were higher in males in the neutrophil area and higher in females in the lymphocyte area, but age-related partitioning was not required. The forward scattered light intensity in the neutrophil area, lymphocyte area, and monocyte area did not require age-related partitioning in males. CONCLUSION: This study has determined comprehensive age- and sex-specific RIs for CPD parameters, which could help to prove the clinical significance of these parameters in the Sysmex XN-2000.

Recent advances in liquid fuel production from plastic waste via pyrolysis: Emphasis on polyolefins and polystyrene.

The management of plastic waste (PW) has become an indispensable worldwide issue because of the enhanced accumulation and environmental impacts of these waste materials. Thermo-catalytic pyrolysis has been proposed as an emerging technology for the valorization of PW into value-added liquid fuels. This review provides a comprehensive investigation of the latest advances in thermo-catalytic pyrolysis of PW for liquid fuel generation, by emphasizing polyethylene, polypropylene, and polystyrene. To this end, the current strategies of PW management are summarized. The various parameters affecting the thermal pyrolysis of PW (e.g., temperature, residence time, heating rate, pyrolysis medium, and plastic type) are discussed, highlighting their significant influence on feed reactivity, product yield, and carbon number distribution of the pyrolysis process. Optimizing these parameters in the pyrolysis process can ensure highly efficient energy recovery from PW. In comparison with non-catalytic PW pyrolysis, catalytic pyrolysis of PW is considered by discussing mechanisms, reaction pathways, and the performance of various catalysts. It is established that the introduction of either acid or base catalysts shifts PW pyrolysis from the conventional free radical mechanism towards the carbonium ion mechanism, altering its kinetics and pathways. This review also provides an overview of PW pyrolysis practicality for scaling up by describing techno-economic challenges and opportunities, environmental considerations, and presenting future outlooks in this field. Overall, via investigation of the recent research findings, this paper offers valuable insights into the potential of thermo-catalytic pyrolysis as an emerging strategy for PW management and the production of liquid fuels, while also highlighting avenues for further exploration and development.

Circularly Polarized Light Emission from Nonchiral Perovskites Incorporated into Nanoporous Cholesteric Polymer Templates.

Chiral perovskites have garnered significant attention, owing to their chiroptical properties and emerging applications. Current fabrication methods often involve complex chemical synthesis routes. Herein, an alternative approach for introducing chirality into nonchiral hybrid organic-inorganic perovskites (HOIPs) using nanotemplates composed of cholesteric polymeric networks is proposed. This method eliminates the need for additional molecular design. In this process, HOIP precursors are incorporated into a porous cholesteric polymer film, and two-dimensional (2D) HOIPs grow inside the nanopores. Circularly polarized light emission (CPLE) was observed even though the selective reflection band of the cholesteric polymer films containing a representative HOIP deviated from the emission wavelength of the 2D HOIP. This effect was confirmed by the induced circular dichroism (CD) observed in the absorbance band of the HOIP. The observed CPLE and CD are attributed to the chirality induced by the template in the originally nonchiral 2D HOIP. Additionally, the developed 2D HOIP exhibited a long exciton lifetime and good stability under harsh conditions. These findings provide valuable insights into the development and design of innovative optoelectronic materials.

Roles of Inflammatory Biomarkers in Exhaled Breath Condensates in Respiratory Clinical Fields.

BACKGROUND: Exhaled condensates contain inflammatory biomarkers; however, their roles in the clinical field have been under-investigated. METHODS: We prospectively enrolled subjects admitted to pulmonology clinics. We collected exhaled breath condensates (EBC) and analysed the levels of six and 12 biomarkers using conventional and multiplex enzyme-linked immunosorbent assay, respectively. RESULTS: Among the 123 subjects, healthy controls constituted the largest group (81 participants; 65.9%), followed by the preserved ratio impaired spirometry group (21 patients; 17.1%) and the chronic obstructive pulmonary disease (COPD) group (21 patients; 17.1%). In COPD patients, platelet derived growth factor-AA exhibited strong positive correlations with COPD assessment test (ρ=0.5926, p=0.0423) and COPD-specific version of St. George's Respiratory Questionnaire (SGRQ-C) score (total, ρ=0.6725, p=0.0166; activity, ρ=0.7176, p=0.0086; and impacts, ρ=0.6151, p=0.0333). Granzyme B showed strong positive correlations with SGRQ-C score (symptoms, ρ=0.6078, p=0.0360; and impacts, ρ=0.6007, p=0.0389). Interleukin 6 exhibited a strong positive correlation with SGRQ-C score (activity, ρ=0.4671, p=0.0378). The absolute serum eosinophil and basophil counts showed positive correlations with pro-collagen I alpha 1 (ρ=0.6735, p=0.0164 and ρ=0.6295, p=0.0283, respectively). In healthy subjects, forced expiratory volume in 1 second (FEV1)/forced vital capacity demonstrated significant correlation with CC chemokine ligand 3 (CCL3)/macrophage inflammatory protein 1 alpha (ρ=0.3897 and p=0.0068). FEV1 exhibited significant correlation with CCL11/eotaxin (ρ=0.4445 and p=0.0017). CONCLUSION: Inflammatory biomarkers in EBC might be useful to predict quality of life concerning respiratory symptoms and serologic markers. Further studies are needed.

Production of light olefins and monocyclic aromatic hydrocarbons from the pyrolysis of waste plastic straws over high-silica zeolite-based catalysts.

Owing to the ever-increasing generation of plastic waste, the need to develop environmentally friendly disposal methods has increased. This study explored the potential of waste plastic straw to generate valuable light olefins and monocyclic aromatic hydrocarbons (MAHs) via catalytic pyrolysis using high-silica zeolite-based catalysts. HZSM-5 (SiO2/Al2O3:200) exhibited superior performance, yielding more light olefins (49.8 wt%) and a higher MAH content than Hbeta (300). This was attributed to the increased acidity and proper shape selectivity. HZSM-5 displayed better coking resistance (0.7 wt%) than Hbeta (4.4 wt%) by impeding secondary reactions, limiting coke precursor formation. The use of HZSM-5 (80) resulted in higher MAHs and lower light olefins than HZSM-5 (200) because of its higher acidity. Incorporation of Co into HZSM-5 (200) marginally lowered light olefin yield (to 44.0 wt%) while notably enhancing MAH production and boosting propene selectivity within the olefin composition. These observations are attributed to the well-balanced coexistence of Lewis and Brønsted acid sites, which stimulated the carbonium ion mechanism and induced H-transfer, cyclization, Diels-alder, and dehydrogenation reactions. The catalytic pyrolysis of plastic straw over high-silica and metal-loaded HZSM-5 catalysts has been suggested as an efficient and sustainable method for transforming plastic waste materials into valuable light olefins and MAHs.

Effects of chitinase-1 inhibitor in obesity-induced and -aggravated asthma in a murine model.

AIMS: Despite recent investigations on the role of chitinase in asthma, its role in obesity-induced asthma has not been evaluated. Therefore, we investigated the roles of chitin, chitinase-1, and a chitinase-1 inhibitor (compound X, CPX) in a murine model. MAIN METHODS: We assigned C57BL/6 mice to the ovalbumin (OVA) model or obesity model group. In the OVA model, mice received intraperitoneal OVA twice within a 2-week interval and intranasal OVA for 3 consecutive days. Additionally, chitin was intranasally administered for 3 consecutive days, and CPX was intraperitoneally injected three times over 5 days. In the obesity model, a high-fat diet (HFD) was maintained for 13 weeks, and CPX was intraperitoneally injected eight times over 4 weeks. KEY FINDINGS: In the OVA model, chitin aggravated OVA-induced airway hyper-responsiveness (AHR), increased bronchoalveolar lavage fluid (BALF) cell proliferation, increased fibrosis, and increased the levels of various inflammatory cytokines (including chitinase-1, TGF-ß, TNF-α, IL-1 ß, IL-6, IL-4, and IL-13). CPX treatment significantly ameliorated these effects. In the obesity model, HFD significantly increased AHR, BALF cell proliferation, fibrosis, and the levels of various inflammatory cytokines. Particularly, compared to the control group, the mRNA expression of chitinase, chitinase-like molecules, and other molecules associated with inflammation and the immune system was significantly upregulated in the HFD and HFD/OVA groups. Immunofluorescence analysis also showed increased chitinase-1 expression in these groups. CPX significantly ameliorated all these effects in this model. SIGNIFICANCE: This study showed that CPX can be an effective therapeutic agent in asthma, especially, obesity-induced and -aggravated asthma to protect against the progression to airway remodeling and fibrosis.

Life expectancy and healthy life expectancy of Korean registered disabled by disability type in 2014-2018: Korea National Rehabilitation Center database.

BACKGROUND: Conducting a distinct comparison between the life expectancy (LE) and healthy life expectancy (HALE) of people with disabilities (PWDs) and the general population is necessary due to the various environmental and health conditions they encounter. Therefore, this study aimed to develop the life table for PWDs and calculate those of LE and HALE based on sex, severity, and disability types among the registered Korean PWDs. METHODS: We used aggregated data of registered PWDs from the Korea National Rehabilitation Center database between 2014 and 2018. Overall, 345,595 deaths were included among 12,627,428 registered PWDs. First, we calculated the LE for total PWDs and non-disabled people using a standard life table, extending the old age mortality among nine models. Subsequently, we calculated the LE for each type of disability using the relationship between the mortality of total PWDs and those of each type of disability. Finally, HALE was calculated using the Sullivan method for three types as follows: disability-free and perceived health (PH) using the National Survey, and hospitalized for ≥ 7 days using the Korea National Health Insurance System (NHIS) database. RESULTS: The calculated LE/HALE-NHIS (years) at registration in males and females were 81.32/73.32 and 87.38/75.58, 68.54/58.98 and 71.43/59.24, 73.87/65.43 and 78.25/67.51, and 61.53/50.48 and 62.41/49.72 years among non-disabled, total PWDs, mild disabled, and severe disabled, respectively. LE/HALE-NHIS was lowest and highest in respiratory dysfunction and hearing disabilities, respectively. CONCLUSIONS: Males with disabilities had shorter LE and HALE at registration than females, except for those with severe disabilities, and there were variabilities in the LE based on the disability types.

Long-Term Clinical Outcomes of Patients with Chronic Obstructive Pulmonary Disease with Sarcopenia.

BACKGROUND AND OBJECTIVE: Sarcopenia with muscle wasting and weakness is a common occurrence among patients with chronic obstructive pulmonary disease (COPD). We aimed to evaluate the clinical outcomes of sarcopenia in patients with COPD. METHODS: We reviewed the electronic medical records of 71 patients with COPD between 1 January 2012, and 31 December 2018. We longitudinally analyzed clinical outcomes in patients with COPD with and without sarcopenia. RESULTS: Compared to the non-sarcopenia group COPD, the sarcopenia group showed a higher rate of acute exacerbation events of COPD (AE COPD, 84.6% vs. 31.0%, p = 0.001), all-cause mortality (30.8% vs. 5.2%, p = 0.022), and pneumonia occurrence per year (median [first quartile-third quartile]; 0.2 [0.0-1.6] vs. 0.0 [0.0-0.2], p = 0.025). Sarcopenia was an independent risk factor for AE COPD in Cox regression analysis (hazard ratio, 5.982; 95% confidence interval, 1.576-22.704). Hand grip strength was associated with the COPD Assessment Test (CAT) score and annual Charlson's comorbidity index score change. Total skeletal muscle mass index (SMMI) was associated with the modified medical research council dyspnea scale score, CAT score, body mass index, airflow obstruction, dyspnea, and exercise (BODE) index, and alanine transaminase. Trunk SMMI was significantly associated with AE COPD, while appendicular SMMI was associated with BODE index and annual intensive care unit admissions for AE COPD. CONCLUSIONS: Sarcopenia is associated with clinical prognosis, pneumonia occurrence, and the acute exacerbation of COPD requiring intensive care in patients with COPD. Therefore, it is important to carefully monitor sarcopenia development as well as recommend appropriate exercise and nutritional supplementation in patients with COPD.

Low Skeletal Muscle Mass and Clinical Outcomes in Chronic Obstructive Pulmonary Disease.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), decreased muscle mass is a frequently encountered comorbidity in clinical practice. However, the evaluation of muscle mass in patients with COPD in real-world practice is rare. METHODS: We retrospectively reviewed the electronic medical records of all patients with COPD who underwent bioelectrical impedance analysis at least once between January 2011 and December 2021 in three hospitals. Then, we analyzed the performance rate of muscle mass measurement in the patients and the correlation between muscle mass, clinical parameters, and COPD prognosis. RESULTS: Among the 24,502 patients with COPD, only 270 (1.1%) underwent muscle mass measurements. The total skeletal muscle mass index was significantly correlated with albumin, alanine transaminase, and creatinine to cystatin C ratio in patients with COPD (r=0.1614, p=0.011; r=0.2112, p=0.001; and r=0.3671, p=0.001, respectively). Acute exacerbation of COPD (AE COPD) was significantly correlated with muscle mass, especially the truncal skeletal muscle mass index (TSMI) in males (r=-0.196, p=0.007). In the multivariate analysis, TSMI and cystatin C were significant risk factors for AE COPD (hazard ratio, 0.200 [95% confidence interval, CI, 0.048 to 0.838] and 4.990 [95% CI, 1.070 to 23.278], respectively). CONCLUSION: Low muscle mass negatively affects the clinical outcomes in patients with COPD. Despite its clinical significance, muscle mass measurement is performed in a small proportion of patients with COPD. Therefore, protocols and guidelines for the screening of sarcopenia in patients with COPD should be established.

Accumulation of plasmacytoid dendritic cell is associated with a treatment response to DNA-damaging treatment and favorable prognosis in lung adenocarcinoma.

Introduction: Favorable responses to the treatment including immune checkpoint inhibitors (ICIs) have been consistently reported in lung cancer with smoking history. As the tumor microenvironment (TME) may be involved in the treatment response to ICIs, we aimed to investigate the TME of lung cancer with different smoking status. Methods: Lung adenocarcinoma (LUAD) tissue (Tu) and adjacent normal-appearing lung tissue (NL) from current and never smokers were investigated by single-cell RNA sequencing and immunofluorescence and immunohistochemical staining. The clinical implications of identified biomarkers were validated using open-source datasets. Results: The lungs of smokers had an increased proportion of innate immune cells in NL tissues, whereas Tu tissues had a lower proportion of these cells than those of non-smokers. Monocyte-derived macrophages (mono-Mc), CD163-LGMN macrophages, monocyte-derived dendritic cells (DCs), and plasmacytoid DCs (pDCs) were significantly enriched in smokers' Tu. Among these clusters, pDCs, specifically enriched in the Tu of smokers. The expression of representative pDC markers, leukocyte immunoglobulin-like receptor A4 (LILRA4) and Toll-like receptor 9 (TLR9), was increased in the stromal cells of LUAD in patients with a smoking history. In an animal model of lung cancer, ionizing radiation induced robust TLR9 expressing immune cells in peritumoral area. Survival analysis using a TCGA-LUAD dataset indicated that patients overexpressing pDC markers exhibited superior clinical outcomes to age-, sex-, and smoking-matched control groups. Top 25% patients with high TLR9 expression exhibited significantly higher tumor mutational burden than that of low TLR9 expression group (bottom 25% patients) (5.81 mutations/Mb vs 4.36 mutations/Mb; P = 0.0059, Welch's two-sample t-test). Conclusion: There is an increased pDC in the TME of smokers' lung cancer, and the response of pDC to DNA damaging treatment would lead a conducive environment to ICIs containing regimens. These findings suggest that R&D that induces an increase in the activated pDC population is continuously required to enhance therapeutic effectiveness of ICIs-containing therapies in lung cancer.