Factors associated with incomplete resection for large, locally invasive non-small cell lung cancer.

Background: Large, node-negative but locally invasive non-small cell lung cancer (NSCLC) is associated with increased perioperative risk but improved survival if a complete resection is obtained. Factors associated with positive margins in this population are not well-studied. Methods: We performed a retrospective cohort study using National Cancer Database (NCDB) for adult patients with >5 cm, clinically node-negative NSCLC with evidence of invasion of nearby structures [2006-2015]. Patients were classified as having major structure involvement (azygous vein, pulmonary artery/vein, vena cava, carina/trachea, esophagus, recurrent laryngeal/vagus nerve, heart, aorta, vertebrae) or chest wall invasion (rib pleura, chest wall, diaphragm). Our primary outcome was to evaluate factors associated with incomplete resection (microscopic: R1, macroscopic: R2). Kaplan-Meier analysis and cox multivariable regression models were used to evaluate overall survival (OS), 90-day mortality, and factors associated with positive margins. Results: Among 2,368 patients identified, the median follow-up was 33.8 months [interquartile range (IQR), 12.6-66.5 months]. Most patients were white (86.9%) with squamous cell histology (47.3%). Major structures were involved in 26.4% of patients and chest wall invasion was seen in 73.6%. Four hundred and seventy-eight patients (20.2%) had an incomplete resection. Multivariable analysis revealed that black race [hazard ratio (HR) 1.568, 95% confidence interval (CI): 1.109-2.218] and major structure involvement (HR 1.412, 95% CI: 1.091-1.827) was associated with increased risk of incomplete resection and surgery at an academic hospitals (HR 0.773, 95% CI: 0.607-0.984), adenocarcinoma histology (HR 0.672, 95% CI: 0.514-0.878), and neoadjuvant chemotherapy (HR 0.431, 95% CI: 0.316-0.587) were associated with decreased risk of incomplete resection. The 5-year OS was 43.7% in the entire cohort and 28.8% in patients with positive margins and 47.5% in patients with an R0 resection. Positive margin was also associated with a significantly higher 90-day mortality rate (9.9% versus 6.7%). Conclusions: For patients with large, node-negative NSCLC invading nearby structures, R0 resection portends better survival. Treatment at academic centers, adenocarcinoma histology, and receipt of neoadjuvant chemotherapy are associated with R0 resection in this high-risk cohort.

The preparation and dual-mode detection of ascorbic acid based on poly(N-isopropylacrylamide) nanogel with oxidase-like activity.

Nanozymes have recently become a research hotspot because of the advantages of good stability, excellent catalytic performance and easy storage in comparison to natural enzymes. Nanozymes with oxidase-like activity get special attention because they needn't the participation of hydrogen peroxide. In this paper, poly(N-isopropylacrylamide) nanogel with oxidase-like activity was synthesized for the first time. The catalytic mechanism was explored by EPR and UV spectroscopy after adding specific trapping agents of ROS, and the results showed that PNIPAM NG can catalyze O2 to 1O2. In the presence of PNIPAM NG, o-phenylenediamine (OPD) and ascorbic acid (AA) can be oxidized to 2,3-diaminophenazine (oxOPD) and dehydroascorbic acid (DHA), and DHA can further react with OPD to produce a fluorescence substance. The colorimetric and fluorescence detection platforms for AA were constructed based on the above principles. Both platforms have satisfactory results in real samples. The fluorescence platform has better sensitivity and selectivity than the colorimetric platform.

Protective Effects and Mechanisms of Luteolin against Acute Respiratory Distress Syndrome: Network Pharmacology and In vivo and In vitro Studies.

BACKGROUND: Acute Respiratory Distress Syndrome (ARDS) is an acute life-threatening disease, and luteolin has the potential to become a therapeutic agent for ARDS. However, its mechanism of action has not yet been clarified. OBJECTIVE: The present study explored the potential effects and mechanisms of luteolin in the treatment of ARDS through network pharmacology analysis and verified them through biological experiments. METHODS: The potential targets of luteolin and ARDS were obtained from online databases. Functional enrichment and protein-protein interaction (PPI) analyses were performed to explore the underlying molecular mechanisms and to identify hub targets. Molecular docking was used to verify the relationship between luteolin and target proteins. Finally, the effects of luteolin on key signaling pathways and biological processes were verified by in vitro and in vivo experiments. RESULTS: A total of 146 luteolin- and 496 ARDS-related targets were extracted from public databases. The network pharmacological analysis suggested that luteolin could inhibit ARDS through the following potential therapeutic targets: AKT1, RELA, and NFKBIA. Inflammatory and oxidative stress responses were the main biological processes involved, with the AKT/NF-κB signaling pathway being the key signaling pathway targeted by luteolin for the treatment of ARDS. Molecular docking analysis indicated that luteolin had a good binding affinity to AKT1, RELA, and NFKBIA. The in vitro and in vivo experiments revealed that luteolin could regulate the inflammatory response and oxidative stress in the treatment of ARDS by inhibiting the AKT/NF- κB signaling pathway. CONCLUSION: Luteolin could reduce the production of reactive oxygen species and inflammatory factors by inhibiting the AKT/NF-κB signaling pathway, thus reducing apoptosis and attenuating ARDS.

Validation of a novel donor lung scoring system based on the updated lung Composite Allocation Score.

Lung transplantation (LTx) continues to have lower rates of long-term graft survival compared with other organs. Additionally, lung utilization rates from brain-dead donors remain substantially lower compared with other solid organs, despite a growing need for LTx and the significant risk of waitlist mortality. This study aims to examine the effects of using a combination of the recently described novel lung donor (LUNDON) acceptability score and the newly adopted recipient lung Composite Allocation Score (CAS) to guide transplantation. We performed a review of nearly 18 000 adult primary lung transplants from 2015-2022 across the US with retroactive calculations of the CAS value. The medium-CAS group (29.6-34.5) had superior 1-year posttransplant survival. Importantly, the combination of high-CAS (> 34.5) recipients with low LUNDON score (≤ 40) donors had the worst survival at 1 year compared with any other combination. Additionally, we constructed a model that predicts 1-year and 3-year survival using the LUNDON acceptability score and CAS values. These results suggest that caution should be exercised when using marginally acceptable donor lungs in high-priority recipients. The use of the LUNDON score with CAS value can potentially guide clinical decision-making for optimal donor-recipient matches for LTx.

Surfactant-assisted preparation of all-gel-state flexible supercapacitor with remarkable electrochemical performance based on polyaniline-polyacrylamide/sodium alginate hydrogels.

The electrochemical performance of polyaniline-based all-gel-state supercapacitor (AGSSC) is significantly depended on the dispersity and mass loaded of polyaniline (PANI). In this manuscript, inspired by the properties of surfactant, sodium dodecylbenzene sulfonate (SDBS) was introduced to prepare various PANI-polyacrylamide/sodium alginate/SDBS (PANIy-PSSx) AGSSCs. With presence of SDBS, the electrochemical performance of PANIy-PSSx AGSSCs was greatly improved, displaying a trend of initial rise and then decrease with increasing concentration of SDBS from 0 to 0.75 wt%. As the content of SDBS was 0.5 wt%, the resulting PANI1.0-PSS0.5 AGSSC displayed the optimum electrochemical properties with area capacitance and energy density of 913.79 mF/cm2 and 81.23 µWh/cm2, respectively. The capacitance rate of PANI1.0-PSS0.5 AGSSC was still more than 93 % after 2000 cycles of sequential CV scans at the scan rate of 200 mV/s. These data were greatly higher than many reported PANI-based AGSSCs. Moreover, the resultant PANI1.0-PSS0.5 AGSSC could maintain high electrochemical performance even after various operations, such as compression, puncture, fluctuating temperature, bending situations and various voltage windows and series-parallel connections. The resultant PANI1.0-PSS0.5 AGSSC had the wide potentials to satisfy the real application requirements. This study offered a facile strategy for design and preparation of flexible supercapacitor with excellent electrochemical performance.

ß-Sitosterol Enhances Lung Epithelial Cell Permeability by Suppressing the NF-κB Signaling Pathway.

BACKGROUND: The dysregulation between pro-inflammatory and anti-inflammatory responses during sepsis is a crucial factor in driving sepsis progression. Acute lung injury (ALI) resulting from excessive production and accumulation of inflammatory mediators in the lungs contributes to impaired lung barrier function. The activation of the NF-κB signaling pathway during inflammation leads to the transcriptional activation of multiple inflammatory genes. Given the plausible impact of NF-κB signaling suppression in mitigating lung injury, substantive evidence demonstrates beta-sitosterol (BS)'s proficient ability to block NF-κB activation. Therefore, the aim of the present investigation was to delve into the impacts of BS in the context of sepsis-induced acute lung injury, employing both a mouse model and a model involving lung epithelial cells. METHODS: Sepsis-induced lung injury was simulated in mice through cecum ligation and puncture (CLP). To emulate injury in murine lung epithelial (MLE-12) cells, an experiment involving lipopolysaccharide (LPS) was administered. Evaluation of alterations in lung tissue permeability encompassed techniques such as lung wet/dry (W/D) mass ratio, Evans blue staining, and quantification of total protein concentration in bronchoalveolar lavage fluid (BALF). Lung tissue histopathological shifts were ascertained via hematoxylin and eosin (HE) staining. Additionally, the concentrations of inflammatory cytokines IL-6 and TNF-α were quantified in every lung tissue and cell group by implementing enzyme-linked immunosorbent assay (ELISA). Protein quantification for signal biomarkers was carried out using Western blotting and immunofluorescence methodologies. In tandem, the assessment of MLE-12 cell permeability was conducted by evaluating fluorescein isothiocyanate (FITC)-dextran extravasation. RESULTS: BS mitigated lung tissue pathologies, reduced inflammatory factors, and lowered tissue and cell permeability. BS inhibited NF-κB signaling and increased claudin-4 and claudin-5 expression, enhancing septic lung epithelial cell permeability. CONCLUSIONS: Through suppressing the NF-κB signaling cascade, BS effectively curtails the levels of inflammatory mediators. Simultaneously, it orchestrates the modulation of claudin-4 and claudin-5 expression, culminating in the augmentation of lung epithelial cell barrier competence, thus improving sepsis-induced lung injury.

Development and validation of a nomogram for predicting deep venous thrombosis in patients with pelvic and acetabular fractures: a retrospective cohort study : Predictive model for pelvic/acetabular fractures.

PURPOSE: To construct a novel nomogram model that can predict DVT and avoid unnecessary examination. METHODS: Patients admitted to the hospital with pelvis/acetabular fractures were included between July 2014 and July 2018. The potential predictors associated with DVT were analyzed using Univariate and multivariable logistic regression analysis. The predictive nomogram was constructed and internally validated. RESULTS: 230 patients were finally enrolled. There were 149 individuals in the non-DVT group and 81 in the DVT group. Following analysis, we obtained the final nomogram model. The risk factors included age (OR, 1.037; 95% CI, 1.013-1.062; P = 0.002), body mass index (BMI) (OR, 1.253; 95% CI, 1.120-1.403; P < 0.001); instant application of anticoagulant after admission (IAA) (OR, 2.734; 95% CI, 0.847-8.829; P = 0.093), hemoglobin (HGB) (OR, 0.970; 95% CI, 0.954-0.986; P < 0.001), D-Dimer(OR, 1.154; 95% CI, 1.016-1.310; P = 0.027) and fibrinogen (FIB) (OR, 1.286; 95% CI, 1.024-1.616; P = 0.002). The apparent C-statistic was 0.811, and the adjusted C-statistic was 0.777 after internal validations, demonstrating good discrimination. Hosmer and Lemeshow's goodness of fit (GOF) test of the predictive model showed a good calibration for the probability of prediction and observation (χ2 = 3.285, P = 0.915; P > 0.05). The decision curve analysis (DCA) and Clinical impact plot (CIC) demonstrated superior clinical use of the nomogram. CONCLUSIONS: An easy-to-calculate nomogram model for predicting DVT in patients with pelvic-acetabular fractures were developed. It could help clinicians to reduce DVT and avoid unnecessary examinations.

Development and validation of the lung donor (LUNDON) acceptability score for pulmonary transplantation.

There is a chronic shortage of donor lungs for pulmonary transplantation due, in part, to low lung utilization rates in the United States. We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients database (2006-2019) and developed the lung donor (LUNDON) acceptability score. A total of 83 219 brain-dead donors were included and were randomly divided into derivation (n = 58 314, 70%) and validation (n = 24 905, 30%) cohorts. The overall lung acceptance was 27.3% (n = 22 767). Donor factors associated with the lung acceptance were age, maximum creatinine, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen, mechanism of death by asphyxiation or drowning, history of cigarette use (≥20 pack-years), history of myocardial infarction, chest x-ray appearance, bloodstream infection, and the occurrence of cardiac arrest after brain death. The prediction model had high discriminatory power (C statistic, 0.891; 95% confidence interval, 0.886-0.895) in the validation cohort. We developed a web-based, user-friendly tool (available at https://sites.wustl.edu/lundon) that provides the predicted probability of donor lung acceptance. LUNDON score was also associated with recipient survival in patients with high lung allocation scores. In conclusion, the multivariable LUNDON score uses readily available donor characteristics to reliably predict lung acceptability. Widespread adoption of this model may standardize lung donor evaluation and improve lung utilization rates.

Assessment of the urban waterlogging resilience and identification of its driving factors: A case study of Wuhan City, China.

With rapid urbanization and extreme rainstorm events associated with climate change, urban waterlogging has become one of the most frequent and severe disasters globally. In this study, a multi-dimensional and multi-process index system based on the Pressure-State-Response (PSR) framework was developed to measure the level of urban waterlogging resilience (UWR). The spatial distribution of UWR on a block scale was explored based on the entropy weight method with the natural breakpoint method (EWM-NBM) in the central district of Wuhan City, China. In addition, the effects of the runoff control facilities and early warning measures on UWR were also quantified. Further, the Geodetector was used to investigate the main driving factors of UWR and their interactions. Results showed that the constructed index system for UWR based on the PSR framework performed reasonably, and the EWM-NBM was validated to be effective in the integrated assessment. In terms of the validation results, 82.72 % of the recorded waterlogging points belonged to high and very-high risk levels. The spatial heterogeneity of UWR was significant in the study area where the higher-level UWR mainly appears in the areas near the undeveloped suburban and water bodies (lakes and rivers), and the lower-level UWR was concentrated in central urban areas with more impervious surfaces. There was a clear increasing trend in UWR after the implementation of runoff control facilities and early warning measures, but its spatial distribution remained almost invariant. Among all the indexes, the impervious surface percentage had the strongest (69.58 %) explanatory ability for the UWR, and mean annual precipitation (15.51 %), GDP (14.03 %), and population density (11.98 %) also demanded attention. Most driving factors of UWR showed nonlinear interactions. This research could provide a benchmark for urban planning to enhance UWR to mitigate the waterlogging within the main urban area.

Acinar cell carcinoma with PRKAR1A and PTEN alterations and paraneoplastic panniculitis.

Pancreatic acinar cell carcinoma is a rare type of pancreatic malignancy, which can be confused with pancreatic neuroendocrine neoplasm. Here, we describe a woman in her 80s who presented with abdominal pain and bilateral lower extremity panniculitis. She underwent surgery for a presumed diagnosis of neuroendocrine tumour with PTEN and PRKAR1A alterations; 19 months, later, a recurrence of her pancreatic malignancy was discovered. The patient underwent repeat resection and this time immunohistochemical staining confirmed the diagnosis of acinar cell carcinoma. Staining for acinar cell carcinoma should be prompted based on clinical suspicion in context of PTEN or PRKAR1A mutation when appropriate.

A novel fluorescent probe of alkyne compounds for putrescine detection based on click reaction.

Putrescine is a toxic biogenic amine produced in the process of food spoilage, and a high concentration of biogenic amines in foods will cause health problems such as abnormal blood pressure, headaches and tachycardia asthma/worsening asthma. The detection of putrescine is necessary. However, traditional putrescine detection requires specialized instruments and complex operations. To detect putrescine quickly, sensitively and accurately, we designed and successfully prepared a fluorescent probe (DPY) with active alkynyl groups. DPY takes p-dimethoxybenzene as the raw material, adding a highly active alkyne group. It is stable in experimental pH (∼7) because the UV-vis absorption and fluorescence emission spectra in pH = 3-12 have little change. The fluorescence intensity of DPY decreased only about 1% under the irradiation of 420 nm within 2 h, showing its better photostability. DPY has a high selectivity to putrescine because of the amino-alkyne click reaction without any catalyst in presence of different biogenic amines. The obvious response to putrescine was found in 30 seconds at room temperature. The mechanism between DPY and putrescine was investigated before and after adding putrescine by 1H NMR spectra and the Job plot. The results indicated a typical 1 : 1 stoichiometry between the DPY and DAB. Furthermore, the higher sensitivity of DPY to putrescine was obtained with the detection of limit (LOD) of 3.19 × 10-7 mol L-1, which was better than that of the national standard (2.27 × 10-5 mol L-1). The novel fluorescent probe was successfully applied to beer samples to detect putrescine. The proposed strategy is expected to provide some guidance for the development of some new ways to detect food security.

Arctigenin attenuates paraquat-induced human lung epithelial A549 cell injury by suppressing ROS/p38 mitogen-activated protein kinases-mediated apoptosis.

BACKGROUND: Paraquat (PQ)-induced acute lung injury (ALI) and pulmonary fibrosis are common diseases with high mortality but without effective antidotes in emergency medicine. Our previous study has proved that arctigenin suppressed pulmonary fibrosis induced by PQ. We wondered whether arctigenin could also have a protective effect on PQ-induced ALI. METHODS: A PQ-induced A549 cell injury model was used, and the effect of arctigenin was determined by a cell counting kit-8 (CCK-8) cell viability assay. In addition, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) staining assays and mitochondrial membrane potential assays were performed to evaluate the level of cell apoptosis. The generation of reactive oxygen species (ROS) was reflected by dihydroethidium (DHE) staining and a 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) assay. Moreover, immunoblotting studies were used to assess the expression of mitogen-activated protein kinases (MAPKs) and p38 MAPK. RESULTS: Arctigenin attenuated PQ-induced inhibition of A549 cell viability in a dose-dependent manner. Arctigenin also significantly reduced PQ-induced A549 cell apoptosis, as reflected by the TUNEL assay and mitochondrial membrane potential assay, which may result from suppressed ROS/p38 MAPK signaling because we found that arctigenin dramatically suppressed ROS generation and p38 MAPK phosphorylation. CONCLUSION: Arctigenin could attenuate PQ-induced lung epithelial A549 cell injury in vitro by suppressing ROS/p38 MAPK-mediated cell apoptosis, and arctigenin might be considered a potential candidate drug for PQ-induced ALI.

A comparison of outcomes after lung transplantation between European and North American centers.

BACKGROUND: With advancements in basic science and clinical medicine, lung transplantation (LT) has evolved rapidly over the last three decades. However, it is unclear if significant regional variations exist in long-term outcomes after LT. METHODS: To investigate potential differences, we performed a retrospective, comparative cohort analysis of adult patients undergoing deceased donor single or double LT in North America (NA) or Europe between January 2006 and December 2016. Data up to April 2019 were abstracted from the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Registry. We compared overall survival (OS) between North American and European LT centers in a propensity score matched analysis. RESULTS: In 3,115 well-matched pairs, though 30-day survival was similar between groups (NA 96.2% vs Europe 95.4%, p = 0.116), 5-year survival was significantly higher in European patients (NA 60.1% vs Europe 70.3%, p < 0.001). CONCLUSIONS: This survival difference persisted in a sensitivity analysis excluding Canadian patients. Prior observations suggest that these disparities are at least partly related to better access to care via universal healthcare models prevalent in Europe. Future studies are warranted to confirm our findings and explore other causal mechanisms. It is likely that potential solutions will require concerted efforts from healthcare providers and policymakers.

Comparison of standard and penalized logistic regression in risk model development.

Objective: Regression models are ubiquitous in thoracic surgical research. We aimed to compare the value of standard logistic regression with the more complex but increasingly used penalized regression models using a recently published risk model as an example. Methods: Using a standardized data set of clinical T1-3N0 esophageal cancer patients, we created models to predict the likelihood of unexpected pathologic nodal disease after surgical resection. Models were fitted using standard logistic regression or penalized regression (ridge, lasso, elastic net, and adaptive lasso). We compared the model performance (Brier score, calibration slope, C statistic, and overfitting) of standard regression with penalized regression models. Results: Among 3206 patients with clinical T1-3N0 esophageal cancer, 668 (22%) had unexpected pathologic nodal disease. Of the 15 candidate variables considered in the models, the key predictors of nodal disease included clinical tumor stage, tumor size, grade, and presence of lymphovascular invasion. The standard regression model and all 4 penalized logistic regression models had virtually identical performance with Brier score ranging from 0.138 to 0.141, concordance index ranging from 0.775 to 0.788, and calibration slope from 0.965 to 1.05. Conclusions: For predictive modeling in surgical outcomes research, when the data set is large and the outcome of interest is relatively frequent, standard regression models and the more complicated penalized models are very likely to have similar predictive performance. The choice of statistical methods for risk model development should be on the basis of the nature of the data at hand and good statistical practice, rather than the novelty or complexity of statistical models.

Minimum Volume Standards for Surgical Care of Early-Stage Lung Cancer: A Cost-Effectiveness Analysis.

BACKGROUND: Multiple stakeholders have advocated for minimum volume standards for complex surgical procedures. The Leapfrog Group recommends that patients with non-small cell lung cancer (NSCLC) receive surgical resection at hospitals that perform at least 40 lung resections annually. However, the cost-effectiveness of this paradigm is unknown. METHODS: A cost-effectiveness analysis was performed on 90-day and 5-year horizons for patients with clinical stage I NSCLC undergoing surgical resection at hospitals stratified by Leapfrog standard. Model inputs were derived from either the literature or a propensity score-matched cohort using the National Cancer Database. For the 5-year horizon, we simulated using a Markov model with 1-year cycle. Incremental cost-effectiveness ratio (ICER) was calculated to evaluate cost-effectiveness. RESULTS: For the 90-day horizon, resection at a Leapfrog hospital was more costly ($25 567 vs $25 530) but had greater utility (0.185 vs 0.181 quality-adjusted life-years), resulting in an ICER of 10 506. Similarly, for the 5-year horizon, resection at a Leapfrog hospital was more costly ($26 600 vs $26 495) but more effective (3.216 vs 3.122 quality-adjusted life-years), resulting in an ICER of 1108. When the costs for long-distance travel, lodging, and loss of productivity for caregivers were factored in, the ICER was 20 499 during the 5-year horizon for resection at Leapfrog hospitals. Using a willingness-to-pay threshold of $50 000, resection at a Leapfrog hospital remained cost-effective. CONCLUSIONS: Receiving surgery for clinical stage I NSCLC at hospitals that meet Leapfrog volume standards is cost-effective. Payers and policymakers should consider supporting patient and caregiver travel to higher volume institutions for lung cancer surgery.

Phosphatidylserine-Specific Phospholipase A1 Alleviates Lipopolysaccharide-Induced Macrophage Inflammation by Inhibiting MAPKs Activation.

Macrophages are a key in innate immune responses and play vital roles in homeostasis and inflammatory diseases. Phosphatidylserine-specific phospholipase A1 (PS-PLA1) is a specific phospholipase which hydrolyzes fatty acid from the sn-1 position of phosphatidylserine (PS) to produce lysophosphatidylserine (lysoPS). Both PS and lysoPS are associated with activation of immune cells including macrophages. However, the effect of PS-PLA1 on macrophage inflammation remains unclear. The purpose of this study is to evaluate the role of PS-PLA1 in lipopolysaccharide (LPS)-induced macrophage inflammation. Alterations of PS-PLA1 expression in LPS-stimulated RAW264.7 macrophages were investigated via Western blot. PS-PLA1 stable knockdown and overexpression RAW264.7 cell lines were generated by infecting cells with appropriate lentiviral vectors, respectively. PS-PLA1 expression was found to be dramatically upregulated in RAW264.7 macrophages after LPS stimulation. PS-PLA1 knockdown promotes while PS-PLA1 overexpression ameliorates the release of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and nitric oxide from RAW264.7 cells and M1 macrophage polarization. Additionally, PS-PLA1 knockdown facilitates phosphorylation of p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), while PS-PLA1 overexpression attenuates their phosphorylation. Moreover, mitogen-activated protein kinase (MAPK) inhibitors block the release of TNF-α and IL-1ß in PS-PLA1 knockdown RAW264.7 cells after LPS stimulation. These findings suggest PS-PLA1 ameliorates LPS-induced macrophage inflammation by inhibiting MAPKs activation, and PS-PLA1 might be considered as a target for modulating macrophage inflammation.

Mitoquinone mitigates paraquat-induced A549 lung epithelial cell injury by promoting MFN1/MFN2-mediated mitochondrial fusion.

Paraquat (PQ) poisoning often leads to severe lung injuries, in which the mitochondria damage plays a critical role. Mitoquinone (MitoQ), a newly designed mitochondria-targeted antioxidant, has been proved for its benefit in mitochondria protection. However, the role of MitoQ in PQ-induced lung injury remains unclear. Thus, this study was performed to investigate the effect of MitoQ on PQ-induced lung injury and its underlying mechanisms. Our work showed that PQ caused the inhibition of A549 lung epithelial cell viability in a dose-dependent manner, while MitoQ remarkably mitigated the PQ-induced cell viability suppression. Besides this, PQ-mediated apoptosis of A549 cells was significantly attenuated by MitoQ, as indicated by the TUNEL assay and mitochondria membrane potential assay. Moreover, the intracellular reactive oxygen species (ROS) production was also dramatically suppressed when cotreated MitoQ with PQ. This could be ascribed to enhanced mitochondrial fusion mediated by Mitofusin 1 (MFN1)/Mitofusin 2 (MFN2), because MitoQ preserved mitochondrial network integrity, as reflected by MitoTracker staining, and MitoQ also increased the expression of MFN1/MFN2 in A549 cells after PQ treatment. Our data suggested MitoQ mitigated PQ-induced lung epithelial cell injury by promoting MFN1/MFN2-mediated mitochondrial fusion, and MitoQ might be a potential candidate drug for the treatment of PQ-induced lung injury.

Interference with connective tissue growth factor attenuated fibroblast-to-myofibroblast transition and pulmonary fibrosis.

Background: The aberrant activation and phenotype shift of resident fibroblasts in lung tissues via fibroblast-to-myofibroblast transition (FMT) is considered a pivotal step in pulmonary fibrogenesis, resulting in excessive extracellular matrix (ECM) production and deposition. However, the molecular mechanisms regulating FMT and lung fibrosis are still unclear. Connective tissue growth factor (CTGF) has been reported to be both an ECM protein and a versatile signaling molecule that is involved in multiple pathophysiological contexts, especially fibrosis. The relationship between CTGF, FMT, and lung fibrosis has not yet been well defined. Methods: In this study, a pulmonary fibrosis (PF) rat model and FMT cell model induced by paraquat (PQ) were established to explore the relevant regulatory mechanisms in vivo and in vitro. Results: The results showed that the CTGF was highly activated and was a mediator of canonical Wnt signaling during FMT and PF. The inhibition of the CTGF by small-interfering ribonucleic acid decreased the expression of FMT markers, including α-smooth muscle actin, vimentin, and collagen I, inhibited the activated Wnt signaling pathway, and ameliorated lung fibrosis. Conclusions: Our findings showed that CTGF was the key effector of the FMT and fibrotic changes, and emphasized the therapeutic potential of the inhibitor or monoclonal antibody against CTGF for PF.

A study on coconut fatty acid diethanolamide-based polyurethane foams.

The possibility of using coconut fatty acid diethanolamide, a derivate from coconut oil as a bio-based polyol for the synthesis of polyurethane foam was explored. The intrinsic tertiary amine moiety in this polyol (p-CFAD) endowed an auto-catalytic effect in the synthesis process of polyurethane foams, combined with a shorter cream and gelation time compared to the fossil-based polyol 3152. H-nuclear magnetic resonance (1H-NMR) and Fourier transform infrared spectrometry (FTIR) were conducted to characterize the chemical structural features of the p-CFAD, and rheology measurement showed the shear-thinning behavior due to the branched structure. A thermal conductivity comparable to the commercial rigid polyurethane foam was achieved when 40wt% fossil-based polyol 3152 was substituted with the bio-based p-CFAD. With the increased content of the p-CFAD, a transition of the physical properties from rigid PU foam to soft PU foam was observed. Scanning electron microscopy (SEM) revealed the occurrence of the interconnected pores on the cell walls with the increase of the added p-CFAD, implying the possibility of regulating the cellular structure and foam properties via the incorporation of the p-CFAD. Results showed the feasibility of using p-CFAD as a potential polyol in the development of bio-based polyurethane foams with high performance.