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We introduce a two-pronged strategy comprising focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening and long-circulating biodegradable nanoparticles (NPs) for systemic delivery of nucleic acids to the brain. Biodegradable poly(ß-amino ester) polymer-based NPs were engineered to stably package various types of nucleic acid payloads and enable prolonged systemic circulation while retaining excellent serum stability. FUS was applied to a predetermined coordinate within the brain to transiently open the BBB, thereby allowing the systemically administered long-circulating NPs to traverse the BBB and accumulate in the FUS-treated brain region, where plasmid DNA or mRNA payloads produced reporter proteins in astrocytes and neurons. In contrast, poorly circulating and/or serum-unstable NPs, including the lipid NP analogous to a platform used in clinic, were unable to provide efficient nucleic acid delivery to the brain regardless of the BBB-opening FUS. The marriage of FUS-mediated BBB opening and the long-circulating NPs engineered to copackage mRNA encoding CRISPR-associated protein 9 and single-guide RNA resulted in genome editing in astrocytes and neurons precisely in the FUS-treated brain region. The combined delivery strategy provides a versatile means to achieve efficient and site-specific therapeutic nucleic acid delivery to and genome editing in the brain via a systemic route.

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BACKGROUND: The operative outcomes of thoracoabdominal aortic aneurysms (TAAAs) are challenged by high operative mortality and disabling complications. This study aimed to explore the baseline clinical, anatomical, and procedural risk factors that impact early and late outcomes following open repair of TAAAs. METHODS: We reviewed the medical records of 290 patients who underwent open repair of TAAAs between 1992 and 2020 at a tertiary referral center. Determinants of early mortality (within 30 days or in hospital) were analyzed using multivariable logistic regression models, while those of overall follow-up mortality were explored using multivariable Cox proportional hazards models and landmark analyses. RESULTS: The rates of early mortality and spinal cord deficits were 13.1% and 11.0%, respectively, with Crawford extent II showing the highest rates. In the logistic regression models, older age (P < 0.001), high cardiopulmonary bypass (CPB) time (P < 0.001), and low surgical volume of the surgeon (P < 0.001) emerged as independent factors significantly associated with early mortality. During follow-up (median, 5.0 years; interquartile range, 1.1-7.6 years), 82 late deaths occurred (5.7%/patient-year). Cox proportional hazards models demonstrated that older age (P < 0.001) and low hemoglobin level (P = 0.032) were significant risk factors of overall mortality, while the landmark analyses revealed that the significant impacts of low surgical volume (P = 0.017), high CPB time (P = 0.002), and Crawford extent II (P = 0.017) on mortality only remained in the early postoperative period, without significant late impacts (all P > 0.05). CONCLUSION: There were differential temporal impacts of perioperative risk variables on mortality in open repair of TAAAs, with older age and low hemoglobin level having significant impacts throughout the postoperative period, and low surgical volume, high CPB time, and Crawford extent II having impacts in the early postoperative phase.

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This study aims to provide a meta-synthesis of qualitative studies examining the perceptions and experiences of nurses who cared for patients in dedicated COVID-19 hospitals in South Korea. We searched key health databases (RISS, KISS, KMbase, NDSL, KoreaMed, DBpia, PubMed, CINAHL, and Cochrane) from September to November 2023. We reviewed and analyzed articles using a thematic synthesis approach. The quality of the studies was ascertained using the Critical Appraisal Skills Program checklist for qualitative research. Ultimately, 13 studies involving 219 nurses were included in the final review. Six major themes and thirteen subthemes emerged. During the unexpected COVID-19 pandemic, nurses were able to overcome difficult situations through their interactions with patients, sense of a professional mission, and commitment to nursing. Most importantly, they persevered through their collaboration and closeness with fellow nurses, despite confusion about their professional identity, the ethical dilemmas they faced in patient care, and the conflicting attitudes of their social support system. To prepare for future infectious disease outbreaks, a multifaceted support system should be established to enable nurses to have positive interactions with their families, colleagues, and patients, which have become central to their resilience.

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Background@#Tumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates. @*Methods@#This study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis. @*Results@#The patients with STAS had a shorter survival time than those without STAS (P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression. @*Conclusion@#In LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS.

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BACKGROUND: In the era of transcatheter aortic valve implantation, this study was conducted to investigate the current trend of aortic valve procedures in Korea and to evaluate the early and mid-term outcomes of isolated surgical aortic valve replacement (SAVR) using bioprosthetic valves in contemporary Korea. METHODS: Contemporary outcomes of isolated bioprosthetic SAVR in Korea were analyzed using the datasets on a multicenter basis. Patients who underwent isolated SAVR using bioprostheses from June 2015 to May 2019 were included, and those with concomitant cardiac procedures, SAVR with mechanical valve, or SAVR for infective endocarditis were excluded. A total of 456 patients from 4 large-volume centers were enrolled in this study. Median follow-up duration was 43.4 months. Early postoperative outcomes, mid-term clinical outcomes, and echocardiographic outcomes were evaluated. RESULTS: Mean age of the patients was 73.1 ± 7.3 years, and EuroSCORE II was 2.23 ± 2.09. The cardiopulmonary bypass time and aortic cross-clamp times were median 106 and 76 minutes, respectively. SAVR was performed with full median sternotomy (81.8%), right thoracotomy (14.7%), or partial sternotomy (3.5%). Operative mortality was 1.8%. The incidences of stroke and permanent pacemaker implantation were 1.1% and 1.1%, respectively. Paravalvular regurgitation ≥ mild was detected in 2.6% of the patients. Cumulative incidence of all-cause mortality at 5 years was 13.0%. Cumulative incidences of cardiovascular mortality and bioprosthetic valve dysfunction at 5 years were 7.6% and 6.8%, respectively. CONCLUSION: The most recent data for isolated SAVR using bioprostheses in Korea resulted in excellent early and mid-term outcomes in a multicenter study.

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This study aimed to confirm the relationship between resilience, meaning in life, and post-traumatic growth (PTG) among nurses during the COVID-19 pandemic. In particular, the mediating effect of meaning in life on the relationship between resilience and PTG was examined. A cross-sectional descriptive research design was used. The participants were 220 nurses at COVID-19-designated hospitals in Seoul. Descriptive statistics, a t-test, ANOVA, Pearson's correlation coefficient analysis, hierarchical regression, and SPSS PROCESS macro (Model 4) were used for data analyses. As a result of the study, resilience and meaning in life each had a significant positive effect on PTG. In addition, the indirect effect of meaning in life was significant, suggesting that meaning in life partially mediated the relationship between resilience and PTG. The results indicate that nurses' resilience directly contributes to the improvement of PTG, and this relationship is further strengthened indirectly through the presence of meaning in life. Therefore, it is suggested that strategies should be developed to enhance resilience and promote a sense of meaning in the profession in order to support the mental health and foster growth among nurses.

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(1) Background: Digital addiction has been a global concern, with college students becoming increasingly vulnerable to it. The detrimental psycho-physiological effects of digital addiction have raised concerns regarding college students' health. This descriptive correlational study was conducted to evaluate the prevalence of digital addiction and identify influencing factors among college students, such as body shape satisfaction, time management, and psychological health. (2) Methods: Data were collected from 199 students at a university in Seoul, South Korea, from 30 May to 13 June 2023. The Digital Addiction Scale (DAS), Time Structure Questionnaire (TSQ), General Health Questionnaire (GHQ), and Body Shape Questionnaire (BSQ) were used for the assessment. Data (N = 199) were analyzed using descriptive statistics, one-way ANOVA, Pearson's correlation coefficient, and stepwise multiple regression. (3) Results: The mean score for digital addiction was 54 ± 12, with scores ranging from 23.0 to 89.0. Digital addiction had a significant positive correlation with body shape satisfaction (r = 0.156, p = 0.028) and a negative correlation with time management (r = -0.500, p < 0.001). In the stepwise multiple regression model of digital addiction (adjusted R2 = 0.285, p < 0.001), subfactors of body shape satisfaction (fear of fatness ß = -0.280, body dissatisfaction ß = 0.401) and time management (effective organization ß = -0.211, persistence ß = -0.209, past orientation ß = -0.165) were statistically significant. (4) Conclusions: Body shape satisfaction and time management are important factors influencing digital addiction among college students. However, it does not establish a direct causal relationship. The findings indicate that there is a statistical association or connection between these factors, but they do not definitively state that body shape satisfaction or time management directly cause digital addiction. To decrease digital addiction in this population, interventions should aim to improve body shape satisfaction and time management.

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INTRODUCTION: Numerous delivery strategies, primarily novel nucleic acid delivery carriers, have been developed and explored to enable therapeutically relevant lung gene therapy. However, its clinical translation is yet to be achieved despite over 30 years of efforts, which is attributed to the inability to overcome a series of biological barriers that hamper efficient nucleic acid transfer to target cells in the lung. AREAS COVERED: This review is initiated with the fundamentals of nucleic acid therapy and a brief overview of previous and ongoing efforts on clinical translation of lung gene therapy. We then walk through the nature of biological barriers encountered by nucleic acid carriers administered via respiratory and/or systemic routes. Finally, we introduce advanced strategies developed to overcome those barriers to achieve therapeutically relevant nucleic acid delivery efficiency in the lung. EXPERT OPINION: We are now stepping close to the clinical translation of lung gene therapy, thanks to the discovery of novel delivery strategies that overcome biological barriers via comprehensive preclinical studies. However, preclinical findings should be cautiously interpreted and validated to ultimately realize meaningful therapeutic outcomes with newly developed delivery strategies in humans. In particular, individual strategies should be selected, tailored, and implemented in a manner directly relevant to specific therapeutic applications and goals.

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Purpose: This study aimed to analyze interventions for bereaved families and evaluate their effectiveness, with the ultimate goal of supporting evidence-based nursing for bereaved families. Methods: Research trends were identified based on a search of domestic databases from January 2000 to December 2022, and a meta-analysis was conducted on interventions for bereaved families. Forty-five papers were selected, and information was extracted on participants, research design, and interventions. A meta-analysis of seven papers was performed, and the effect size was calculated. Results: Fourteen papers dealt with interventions for middle-aged women who had lost their spouses, 20 used qualitative research methods, and 20 were on art therapy programs. Thirty studies had fewer than 10 participants, and most interventions had 60~120 minutes per session and 9~16 sessions in total. There were seven randomized controlled trials, and all studies included in the quality evaluation showed a low risk of bias. Four papers measured grief as an outcome, and the effect size was -1.9577 (95% CI -2.9206 to -0.9947), indicating that the treatment significantly decreased grief (P<0.001). Six papers measured depression as an outcome, and the effect size was -1.6775 (95% CI -2.1835 to -1.1716), showing that the treatment significantly decreased depression (P<0.001). Conclusion: Intervention programs for bereaved families were shown to be effective in relieving grief and depression. However, programs should be developed that target middle-aged men who have lost their spouses and children who have lost their parents. Randomized controlled trials should also be conducted on interventions to reduce grief and depression.

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Objective: Genetic aortopathy, if left untreated, leads to aortic catastrophe in most affected individuals. We sought to determine the genetic mutation patterns and detection rates in patients with aortopathy and their families with a systematic screening protocol. Methods: In 2016 to 2020, patients with aortic dissection or root aneurysm (Z score ≥2) and their first-degree relatives were enrolled in a prospective registry at a tertiary referral center. The individuals underwent systematic single- or multi-gene panel testing depending on clinical presentations. Results: Among 575 enrolled individuals (mean age, 46.6 ± 14.5 years; 203 women), 346 (60.2%) underwent genetic testing. Rates of relevant gene mutations identified were 39.4% (91/231), 27.1% (54/199) and 72.4% (n = 105) in aneurysm, dissection, and family screening groups, respectively (P < .001). Mutated genes frequently identified were FBN1 (n = 199; Marfan), TGFBR1/2 or SMAD3 (n = 14; Loeys-Dietz), COL3A1/COL5A2 (n = 15; Ehlers-Danlos), and ACTA2 (n = 10). After enrollment, 123 aortic surgeries were performed in 117 patients (20.3%) including 15 family members, with resultant operative mortality of 0.8% (n = 1). In logistic regression analysis, systemic score in Ghent nosology was the only significant factor associated with positive gene mutation (odds ratio, 14.81; 95% confidence interval, 6.87-31.96), and its 3.5 point cutoff showed the best predictive value with 78.2% sensitivity and 87.2% specificity. Conclusions: Genetic aortopathy was identified in a considerable proportion of patients with aortopathy and their family members by systematic genetic testing. This strategy is recommended for timely diagnosis and proactive management of genetic aortopathy.

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This exploratory study aimed to identify factors that may influence nurses' turnover intentions during the COVID-19 pandemic. The data were collected during January 2023 from 250 nurses and analyzed using descriptive statistics, t-test, ANOVA, Scheffe, Pearson's correlation, and multiple regression analysis. Among the sociodemographic and clinical characteristics, nursing care and working with personal protective equipment significantly impacted the turnover intention. Among the independent variables, compassion satisfaction, burnout, effort-reward ratio, and psychological distress were significant, with an explanatory power of 43.3%. Among the subjects, 86.4% (216 people) showed a moderate or high burnout level because of the COVID-19 pandemic, and burnout seemed to have a significant impact on turnover intention. Therefore, to lower the turnover intention of nurses, burnout should be prevented, and managers should create an environment where nurses can receive a balanced reward for their efforts.

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BACKGROUND/AIMS: Recombinant adeno-associated viruses (rAAV) are an important tool for lung targeted gene therapy. Substitution of tyrosine with phenylalanine residues (Y-F) in the capsid have been shown to protect the AAV vector from ubiquitin/proteasome degradation, increasing transduction efficiency. We tested the mutant Y733F-AAV8 vector for mucus diffusion, as well as the safety and efficacy of pigment epithelium-derived factor (PEDF) gene transfer to the lung. METHODS: For this purpose, Y733F-AAV8-PEDF (1010 viral genome) was administered intratracheally to C57BL/6 mice. Lung mechanics, morphometry, and inflammation were evaluated 7, 14, 21, and 28 days after injection. RESULTS: The tyrosine-mutant AAV8 vector was efficient at penetrating mucus in ex vivo assays and at transferring the gene to lung cells after in vivo instillation. Increased levels of transgene mRNA were observed 28 days after vector administration. Overexpression of PEDF did not affect in vivo lung parameters. CONCLUSION: These findings provide a basis for further development of Y733F-AAV8-based gene therapies for safe and effective delivery of PEDF, which has anti-angiogenic, anti-inflammatory and anti-fibrotic activities and might be a promising therapy for lung inflammatory disorders.

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Although optimal medical therapy (OMT) after coronary revascularization is advocated for intensive secondary prevention, its criteria and effect on long-term outcomes are uncertain. Using data from the ASAN-Multivessel (Asan Medical Center-Multivessel Revascularization) registry, we identified 8,311 patients who underwent coronary artery bypass grafting (CABG) (n = 3,115) or percutaneous coronary intervention (PCI) (n = 5,196). OMT was defined as the combination of minimum of 3 medications in 4 drug classes (antiplatelet drugs, statins, ß blockers, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers). Two primary outcomes were all-cause mortality and serious composite outcome of death, spontaneous myocardial infarction, or stroke at 10 years. Of 8,311 patients, 4,321 (52.0%) followed OMT. In the 3,397 propensity-score-matched cohort, OMT status compared with non-OMT status was significantly associated with a lower risk of all-cause mortality (10.7% vs 18.7%; hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.47 to 0.65) and serious composite outcome (14.5% vs 22.5%, HR 0.635, 95% CI 0.55 to 0.73) at 10 years. The association on 10-year mortality was more prominent in the PCI group (HR 0.45, 95% CI 0.36 to 0.56) than in the CABG group (HR 0.72, 95% CI 0.58 to 0.90) with a significant interaction (p = 0.001). Overall findings were consistent using different OMT criteria (all 4 types of medications). In conclusion, OMT significantly lowered the risks of mortality and major cardiovascular events at 10 years in patients with multivessel revascularization. The OMT impact on mortality was more remarkable in the PCI group than in the CABG group. This work was registered at http://ClinicalTrials.gov (Identifier: NCT02039752).

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We here introduce a novel bioreducible polymer-based gene delivery platform enabling widespread transgene expression in multiple brain regions with therapeutic relevance following intracranial convection-enhanced delivery. Our bioreducible nanoparticles provide markedly enhanced gene delivery efficacy in vitro and in vivo compared to nonbiodegradable nanoparticles primarily due to the ability to release gene payloads preferentially inside cells. Remarkably, our platform exhibits competitive gene delivery efficacy in a neuron-rich brain region compared to a viral vector under previous and current clinical investigations with demonstrated positive outcomes. Thus, our platform may serve as an attractive alternative for the intracranial gene therapy of neurological disorders.

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Messenger RNA (mRNA) is now in the limelight as a powerful tool for treating various human diseases, especially malignant tumors, thanks to the remarkable clinical outcomes of mRNA vaccines using lipid nanoparticle technology during the COVID-19 pandemic. Recent promising preclinical and clinical results that epitomize the advancement in mRNA and nanoformulation-based delivery technologies have highlighted the tremendous potential of mRNA in cancer immunotherapy. mRNAs can be harnessed for cancer immunotherapy in forms of various therapeutic modalities, including cancer vaccines, adoptive T-cell therapies, therapeutic antibodies, and immunomodulatory proteins. This review provides a comprehensive overview of the current state and prospects of mRNA-based therapeutics, including numerous delivery and therapeutic strategies.

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Adeno-associated virus (AAV) vector has shown multiple clinical breakthroughs, but its clinical implementation in inhaled gene therapy remains elusive due to difficulty in transducing lung airway cells. We demonstrate here AAV serotype 6 (AAV6) associated with extracellular vesicles (EVs) and secreted from vector-producing HEK-293 cells during vector preparation (EVAAV6) as a safe and highly efficacious gene delivery platform for inhaled gene therapy applications. Specifically, we discovered that EVAAV6 provided markedly enhanced reporter transgene expression in mucus-covered air-liquid interface (ALI) cultures of primary human bronchial and nasal epithelial cells as well as in mouse lung airways compared to standard preparations of AAV6 alone. Of note, AAV6 has been previously shown to outperform other clinically tested AAV serotypes, including those approved by the FDA for treating non-lung diseases, in transducing ALI cultures of primary human airway cells. We provide compelling experimental evidence that the superior performance of EVAAV6 is attributed to the ability of EV to facilitate mucus penetration and cellular entry/transduction of AAV6. The tight and stable linkage between AAV6 and EVs appears essential to exploit the benefits of EVs given that a physical mixture of individually prepared EVs and AAV6 failed to mediate EV-AAV6 interactions or to enhance gene transfer efficacy.

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BACKGROUND: Some patients have severe aortic valve stenosis (AS) despite a lower degree of aortic valve calcification (AVC). This study compared the clinical features and prognosis of patients undergoing aortic valve replacement (AVR) for severe AS with a low AVC score compared with those with higher AVC scores. METHODS: This study included 1002 Korean patients with symptomatic severe degenerative AS who underwent AVR. We measured AVC score before AVR and defined low AVC as AVC score of <2000 units for male patients and <1300 units for female patients. Patients with bicuspid or rheumatic aortic valve disease were excluded. RESULTS: The mean age was 75.6±7.9 years and 487 patients (48.6%) were female. Mean left ventricular ejection fraction was 59.4%±10.4%, and concomitant coronary revascularisation was performed in 96 patients (9.6%). The median aortic valve calcium score was 3122 units (IQR 2249-4289 units) among male patients and 1756 units (IQR 1192-2572) among female patients. A total of 242 patients (24.2%) had low AVC; they were significantly younger (73.5±8.7 years vs 76.3±7.5 years, p<0.001) and were more likely to be female (59.5% vs 45.1%, p<0.001) and on haemodialysis (5.4% vs 1.8%, p=0.006) than those with high AVC. During a follow-up (median: 3.8 years), the patients with low AVC had significantly higher risk of death from any cause (adjusted HR 1.60, 95% CI 1.02 to 2.52, p=0.04), mostly non-cardiac cause. CONCLUSIONS: Patients with low AVC exhibit distinct clinical characteristics and a higher risk of long-term mortality compared with those with high AVC.

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PURPOSE: This study investigated the effects of healthy lifestyle interventions (HLSIs) on health-related quality of life (HR-QoL) in childhood and adolescent cancer survivors (CACS). METHODS: Major databases were searched for English-language original articles published between January 1, 2000 and May 2, 2021. Randomized controlled trials (RCTs) and non-RCTs were included. Quality was assessed using the revised Cochrane risk-of-bias tool, and a meta-analysis was conducted using RevMan 5.3 software. RESULTS: Nineteen studies were included. Significant effects on HR-QoL were found for interventions using a multi-modal approach (exercise and education) (d=-0.46; 95% confidence interval [CI]=-0.84 to -0.07, p=.02), lasting not less than 6 months (d=-0.72; 95% CI=-1.15 to -0.29, p=.0010), and using a group approach (d=-0.46; 95% CI=-0.85 to -0.06, p=.02). Self-efficacy showed significant effects when HLSIs provided health education only (d=-0.55; 95% CI=-0.92 to -0.18; p=.003), lasted for less than 6 months (d=-0.40; 95% CI=-0.69 to -0.11, p=.006), and were conducted individually (d=-0.55; 95% CI=-0.92 to -0.18, p=.003). The physical outcomes (physical activity, fatigue, exercise capacity-VO2, exercise capacity-upper body, body mass index) revealed no statistical significance. CONCLUSION: Areas of HLSIs for CACS requiring further study were identified, and needs and directions of research for holistic health management were suggested.

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The unique cancer-associated immunosuppression in brain, combined with a paucity of infiltrating T cells, contributes to the low response rate and poor treatment outcomes of T cell-based immunotherapy for patients diagnosed with glioblastoma multiforme (GBM). Here, we report on a self-assembling paclitaxel (PTX) filament (PF) hydrogel that stimulates macrophage-mediated immune response for local treatment of recurrent glioblastoma. Our results suggest that aqueous PF solutions containing aCD47 can be directly deposited into the tumor resection cavity, enabling seamless hydrogel filling of the cavity and long-term release of both therapeutics. The PTX PFs elicit an immune-stimulating tumor microenvironment (TME) and thus sensitizes tumor to the aCD47-mediated blockade of the antiphagocytic "don't eat me" signal, which subsequently promotes tumor cell phagocytosis by macrophages and also triggers an antitumor T cell response. As adjuvant therapy after surgery, this aCD47/PF supramolecular hydrogel effectively suppresses primary brain tumor recurrence and prolongs overall survivals with minimal off-target side effects.

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Silicosis is an irreversible and progressive fibrotic lung disease caused by massive inhalation of crystalline silica dust at workplaces, affecting millions of industrial workers worldwide. A tyrosine kinase inhibitor, nintedanib (NTB), has emerged as a potential silicosis treatment due to its inhibitory effects on key signaling pathways that promote silica-induced pulmonary fibrosis. However, chronic and frequent use of the oral NTB formulation clinically approved for treating other fibrotic lung diseases often results in significant side effects. To this end, we engineered a nanocrystal-based suspension formulation of NTB (NTB-NS) possessing specific physicochemical properties to enhance drug retention in the lung for localized treatment of silicosis via inhalation. Our NTB-NS formulation was prepared using a wet-milling procedure in presence of Pluronic F127 to endow the formulation with nonadhesive surface coatings to minimize interactions with therapy-inactivating delivery barriers in the lung. We found that NTB-NS, following intratracheal administration, provided robust anti-fibrotic effects and mechanical lung function recovery in a mouse model of silicosis, whereas a 100-fold greater oral NTB dose given with a triple dosing frequency failed to do so. Importantly, several key pathological phenotypes were fully normalized by NTB-NS without displaying notable local or systemic adverse effects. Overall, NTB-NS may open a new avenue for localized treatment of silicosis and potentially other fibrotic lung diseases.