Association between Clinical Characteristics and Microbiota in Bronchiectasis Patients Based on Metagenomic Next-Generation Sequencing Technology.

This study aimed to investigate the disparities between metagenomic next-generation sequencing (mNGS) and conventional culture results in patients with bronchiectasis. Additionally, we sought to investigate the correlation between the clinical characteristics of patients and their microbiome profiles. The overarching goal was to enhance the effective management and treatment of bronchiectasis patients, providing a theoretical foundation for healthcare professionals. A retrospective survey was conducted on 67 bronchiectasis patients admitted to The First Hospital of Jiaxing from October 2019 to March 2023. Clinical baseline information, inflammatory indicators, and pathogen detection reports, including mNGS, conventional blood culture, bronchoalveolar lavage fluid (BALF) culture, and sputum culture results, were collected. By comparing the results of mNGS and conventional culture, the differences in pathogen detection rate and pathogen types were explored, and the diagnostic performance of mNGS compared to conventional culture was evaluated. Based on the various pathogens detected by mNGS, the association between clinical characteristics of bronchiectasis patients and mNGS microbiota results was analyzed. The number and types of pathogens detected by mNGS were significantly larger than those detected by conventional culture. The diagnostic efficacy of mNGS was significantly superior to conventional culture for all types of pathogens, particularly in viral detection (p < 0.01). Regarding pathogen detection rate, the bacteria with the highest detection rate were Pseudomonas aeruginosa (17/58) and Haemophilus influenzae (11/58); the fungus with the highest detection rate was Aspergillus fumigatus (10/21), and the virus with the highest detection rate was human herpes virus 4 (4/11). Differences were observed between the positive and negative groups for P. aeruginosa in terms of common scoring systems for bronchiectasis and whether the main symptom of bronchiectasis manifested as thick sputum (p < 0.05). Significant distinctions were also noted between the positive and negative groups for A. fumigatus regarding Reiff score, neutrophil percentage, bronchiectasis etiology, and alterations in treatment plans following mNGS results reporting (p < 0.05). Notably, 70% of patients with positive A. fumigatus infection opted to change their treatment plans. The correlation study between clinical characteristics of bronchiectasis patients and mNGS microbiological results revealed that bacteria, such as P. aeruginosa, and fungi, such as A. fumigatus, were associated with specific clinical features of patients. This underscored the significance of mNGS in guiding personalized treatment approaches. mNGS could identify multiple pathogens in different types of bronchiectasis samples and was a rapid and effective diagnostic tool for pathogen identification. Its use was recommended for diagnosing the causes of infections in bronchiectasis patients.

Clinical and molecular epidemiology of enterovirus D68 from 2013 to 2020 in Shanghai.

Enterovirus D68 (EV-D68) is an emerging pathogen that has caused outbreaks of severe respiratory disease worldwide, especially in children. We aim to investigate the prevalence and genetic characteristics of EV-D68 in children from Shanghai. Nasopharyngeal swab or bronchoalveolar lavage fluid samples collected from children hospitalized with community-acquired pneumonia were screened for EV-D68. Nine of 3997 samples were EV-D68-positive. Seven of nine positive samples were sequenced and submitted to GenBank. Based on partial polyprotein gene (3D) or complete sequence analysis, we found the seven strains belong to different clades and subclades, including three D1 (detected in 2013 and 2014), one D2 (2013), one D3 (2019), and two B3 (2014 and 2018). Overall, we show different clades and subclades of EV-D68 spread with low positive rates (0.2%) among children in Shanghai between 2013 and 2020. Amino acid mutations were found in the epitopes of the VP1 BC and DE loops and C-terminus; similarity analysis provided evidence for recombination as an important mechanism of genomic diversification. Both single nucleotide mutations and recombination play a role in evolution of EV-D68. Genetic instability within these clinical strains may indicate large outbreaks could occur following cumulative mutations.

The Utility of Metagenomic Next-Generation Sequencing (mNGS) in the Management of Patients With Bronchiectasis: A Single-Center Retrospective Study of 93 Cases.

Background: Bronchiectasis is a chronic inflammatory respiratory disease mainly caused by pathogenic infections. However, standard methods of pathogen detection show prolonged cycle durations and unsatisfactory sensitivity and detection rates. Macrogenomic next-generation sequencing (mNGS) emerges as a promising technique for swift, effective, and unbiased pathogen detection and subsequent data interpretation. Methods: Here, a retrospective analysis of 93 patients with suspected bronchiectasis was performed to assess the clinical applicability of mNGS. Bronchoalveolar alveolar lavage fluid (BALF) samples were collected from these subjects, followed by standard assays and mNGS separately. The turnaround time, detection rate, and pathogen identification using mNGS were compared with those of standard methods. Results: mNGS identified a greater number of bacteria (72 vs 16), fungi (26 vs 19), and viruses (14 vs 0) than standard methods. Specifically, the commonly identified bacteria were Haemophilus, Mycobacterium intracellulare, Pseudomonas, and Streptococcus pneumoniae, while the most detected fungi were Aspergillus and the most prevalent viruses were human herpesviruses. Of note, 29 out of 30 patients (96.67%) who received optimized treatment strategies based on mNGS results experienced recovery. Conclusions: Collectively, these findings suggest that mNGS has the potential to improve the diagnosis and treatment of bronchiectasis patients by enabling rapid and precise pathogen detection, which can lead to timely and effective treatment strategies.

Investigation of the Potential Correlation Between RNA-Binding Proteins in the Evolutionarily Conserved MEX3 Family and Non-small-Cell Lung Cancer.

Members of the MEX3 (muscle excess 3) family, uniquely characterised as mRNA binding proteins, play emerging roles in the post-transcriptional regulation of programmed biological processes, including tumour cell death and immune mechanisms, and have been shown to be involved in a variety of diseases. However, the role of MEX3 in non-small cell lung cancer (NSCLC) has not been fully elucidated. In this study, we found no significant changes in the sequence and copy number of the MEX3 gene through analysis using the COSMIC database, revealing its stability during malignancy development. Its expression in NSCLC was examined using the Oncomine™ database, and the prognosis of each member gene was analysed by Kaplan-Meier. The results showed that overexpression of MEX3A, MEX3B, MEX3C and MEX3D was associated with significantly worse OS in patients with LUAD, while overexpression of MEX3D was also associated with significantly worse OS in patients with LUSC. Afterwards, we applied the Tumour Immunology Estimation Resource (TIMER) tool to assess the correlation between different MEX3 and infiltrative immune cell infiltration. Ultimately, we found that most MEX3 members were highly expressed in NSCLC, with high expression suggesting poor prognosis and correlating with immune cell infiltration. The complexity and heterogeneity of NSCLC was understood through MEX3, setting the framework for the prognostic impact of MEX3 in NSCLC patients and the development of new targeted therapeutic strategies in the future.

Self-assembled endogenous DNA nanoparticles for auto-release and expression of the eGFP gene in Bacillus subtilis.

The development of DNA delivery techniques is critical to promote the wider use of deoxyribonucleic acids as cellular transporters. The present study aimed to develop a type of DNA nanoparticle (citZ-box) to automatically load and release cargo. The restriction enzyme can cleave citZ-boxes at pro-designed sites, and the enhanced green fluorescent protein gene (eGFP) can be delivered into the B. subtilis protoplasts by them. The process of eGFP expression is recorded using a confocal microscope over 4 h. Here, multiscaffold and multimodular designs are used for citZ-box assembly with a DAEDALUS module, DX_cage_design and rem (edge_length, 21), to ensure the structure was predicted as B-type DNA. Finally the citZ-box is estimated to be a 50.7 nm cube. The 3D structure of the citZ-box particle is detected to be approximately 50.3 ± 0.3 nm. DNA nanoparticles prepared as citZ-boxes have great potential as drug carriers with automatic loading and releasing abilities.

Response to Omalizumab as an Add-On Therapy in the Treatment of Allergic Asthma in Adult Chinese Patients-A Retrospective Study.

(a) Background: Omalizumab is an anti-IgE humanized monoclonal antibody marketed in China for the conventional treatment of poorly controlled moderate-to-severe allergic asthma. Numerous clinical trials have demonstrated the effectiveness of omalizumab, but the data from studies in actual clinical treatment are still relatively limited. (b) Methods: Thirty-two patients with moderate-to-severe allergic asthma treated with omalizumab on the basis of ICS-LABA (inhaled corticosteroids/long-acting beta2-agonist) were selected. Clinical characteristics before and after treatment were collected to analyze the relationship between changes in serum total IgE levels and peripheral blood EOS (eosinophil) levels, FEV1 (forced expiratory volume in 1 second), PEF (peak expiratory flow), OCS (oral glucocorticoid) dosage, ATC (asthma control test) score, and the number of acute exacerbations and the treatment response, in order to observe the efficacy of omalizumab in addition to primary therapy, and to investigate whether baseline clinical characteristics such as serum total IgE and EOS levels could predict a treatment response. (c) Results: Using the ACT score as an evaluation, 68.75% of patients benefited from omalizumab treatment at the end of 16 weeks. The response group has a reduction in OCS dosage (p-values of 0.026 and 0.039), a significant reduction in ACT scores (both p < 0.001), and a reduction in the number of acute exacerbations (p = 0.034 and 0.025, respectively) after omalizumab treatment. The binary logistics analysis of factors affecting the effectiveness of omalizumab in the treatment of allergic asthma were total serum IgE and the presence of comorbidities (p-values of 0.039 and 0.046, respectively). (d) Conclusions: Combining omalizumab with ICS-LABA for 16 weeks significantly improves asthma symptoms in Chinese adults and can be used as an add-on treatment. In addition, high serum IgE levels and the presence of comorbidities were predictors of its therapeutic efficacy.

Clinical application of metagenomic next-generation sequencing technology in the diagnosis and treatment of pulmonary infection pathogens: A prospective single-center study of 138 patients.

INTRODUCTION: Rapid and accurate pathogen identification is essential for the treatment of pneumonia. Metagenomic next-generation sequencing (mNGS) is a newly developed technology to obtain microbial nucleic acid sequence information quickly, efficiently, and without bias. METHODS: We performed shotgun metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) for pathogen identification in pneumonia in a prospective study with 138 patients from a single center. We compared the results of mNGS with standard methods including culture, staining, and targeted PCR and evaluated the clinical applicability of mNGS. RESULTS: Most of the patients (128/138, 92.75%) were cured or improved. One patient (1/138, 0.72%) died because of acute gastrointestinal bleeding, and 9 patients (9/138, 6.52%) showed no improvement. mNGS identified more bacteria (53 versus 27), fewer fungi (8 versus 31), and more viruses (16 versus 1) than standard methods. In total, treatment in 34 out of 138 cases (24.64%) was adjusted and optimized because of mNGS results. Positive mNGS results contributed to a definitive diagnosis in 23 cases (16.67%), which helped guide treatment decision by either adjusting the antibiotics without de-escalation or continuing the empirical treatment. mNGS also confirmed no active infection in 11 cases (7.97%) allowed for antibiotic de-escalation. CONCLUSION: This prospective clinical study evaluated the clinical utility of mNGS for the diagnosis of pneumonia and showed that mNGS of BALF provides valuable information for effective treatment.

Mycoplasma pneumoniae and Adenovirus Coinfection Cause Pediatric Severe Community-Acquired Pneumonia.

Consolidation is one complication of pediatric severe community-acquired pneumonia (SCAP) that can respond poorly to conservative medical treatment. We investigated the pathogens that cause pediatric SCAP including cases with persistent consolidation that need bronchoscopy intervention. Alveolar lavage fluid (ALF) samples collected from cases admitted to Children's Hospital of Fudan University with SCAP during January 2019 to March in 2019 were retrospectively tested by the RespiFinder 2SMART multiplex PCR (multi-PCR) assay targeting 22 respiratory pathogens. A total of 90 cases and 91 samples were enrolled; 80.0% (72/90) of the cases had pulmonary consolidation and/or atelectasis. All samples were positive with targeted pathogens tested by multi-PCR, and 92.3% (84/91) of the samples were co-detected with pathogens. Mycoplasma pneumoniae (MP) and adenovirus (ADV) as the two dominant pathogens, with the positive rates of 96.7% (88/91) and 79.1% (72/91), respectively. Most of the samples were positive with MP and ADV simultaneously. As a control, 78.0% (71/91) of the samples were positive by conventional tests (CT), in which MP had the detection rate of 63.9% (55/86) by a traditional real-time PCR assay, while ADV were positive in 13.1% (12/91) of the samples by a direct immunofluorescence assay (DFA). In cases with persistent pulmonary consolidation, the positive rates of pathogens by multi-PCR and CT were 100% (72/72) and 81.9% (59/72), respectively. There were no significant differences of MP or ADV positive rates between cases with and without pulmonary consolidation. MP and ADV most prevalent in pediatric SCAP cases required fiberscope intervention, and presented with coinfections dominantly. IMPORTANCE Pathogens that cause pediatric severe community-acquired pneumonia (SCAP) requiring bronchoscopy intervention are understudied. Through this study, we explore the etiology of SCAP form alveolar lavage fluid (ALF) samples by the RespiFinder 2SMART multi-PCR assay. It is observed that high mixed detection rates of Mycoplasma pneumoniae and adenovirus in ALF samples collected from hospitalized SCAP children experienced bronchoscopy intervention. Eighty percent of the cases had pulmonary consolidation and/or atelectasis. The presence of possible coinfection of these two pathogens might contribute to poor clinical anti-infection response. The results of this study might be helpful for the selection of clinical strategies for the empirical treatment of such pediatric SCAP cases.

Serum 8-Hydroxydeoxyguanosine Is a Potential Indicator for the Severity and Prognosis in Patients with Community-Acquired Pneumonia: A Prospective Cohort Study.

Previous studies have demonstrated that 8-hydroxydeoxyguanosine (8-OHdG) exerted key roles in various pulmonary diseases, but the evidence for its role in community-acquired pneumonia (CAP) was lacking. The goal of this research was to evaluate the correlations of serum 8-OHdG with the severity and prognosis among patients with CAP through a prospective cohort study. A total of 239 patients with CAP and 239 healthy participants were enrolled. Fasting blood samples were collected. 8-OHdG and inflammatory cytokines were measured by ELISA. On admission, serum 8-OHdG was significantly increased in patients with CAP compared with control subjects. Besides, serum 8-OHdG was incrementally increased in line with CAP severity scores. Pearson correlative analysis found that serum 8-OHdG was correlated with clinical characteristics and inflammatory cytokines in patients with CAP. Linear and logistic regression analysis showed that serum 8-OHdG was positively associated with CAP severity scores. Furthermore, the prognostic outcomes were tracked. Higher serum 8-OHdG on admission increased the risks for intensive care unit admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stay among patients with CAP. Serum 8-OHdG combination with confusion, respiratory rate, blood pressure, and age ≥65 y or pneumonia severity index had stronger predictive powers for death than single 8-OHdG, CAP severity scores, or several inflammatory cytokines in patients with CAP. These results indicated that serum 8-OHdG is positively associated with the severity and poor prognosis in patients with CAP, demonstrating that 8-OHdG may be involved in the pathophysiology process of CAP.

Epidemiology of Viruses Causing Pediatric Community Acquired Pneumonia in Shanghai During 2010-2020: What Happened Before and After the COVID-19 Outbreak?

INTRODUCTION: Since the global outbreak of COVID-19, there has been a significant reduction in pediatric outpatient and emergency visits for infectious diseases. The purpose of this study was to analyze the changes in respiratory viruses in children with community-acquired pneumonia (CAP) in Shanghai in the past 10 years, especially in the first year after COVID-19. METHODS: We conducted a retrospective, observational study; the results for eight common respiratory viruses (respiratory syncytial virus (RSV), influenza virus A and B, parainfluenza virus 1-3 (PIV), adenovirus (ADV) and human metapneumovirus) tested by direct fluorescent antibody assays in hospitalized CAP cases in Children's Hospital of Fudan University during 2010-2020 were analyzed. RESULTS: Of the 5544 hospitalized CAP patients included in this study, 20.2% (1125/5544) were positive for the eight respiratory viruses. The top three pathogens were RSV, PIV3 and ADV, detected from 9.8% (543/5544), 5.3% (294/5544) and 2.0% (111/5544) of the samples, respectively. RSV had the highest positive rates among children < 2 years old. In 2020, the detection rate of all viruses showed a sharp decline from February to August compared with the previous 9 years. When the Shanghai community reopened in August 2020, the detection rate of eight viruses rebounded significantly in September. CONCLUSIONS: These eight respiratory viruses, especially RSV and PIV, were important pathogens of CAP in Shanghai children in the past 10 years. The COVID-19 pandemic had a significant impact on the detection rates for eight respiratory viruses in children with CAP in Shanghai.

Wobble Editing of Cre-box by Unspecific CRISPR/Cas9 Causes CCR Release and Phenotypic Changes in Bacillus pumilus.

CRISPR-associated Cas9 endonuclease (CRISPR/Cas9) systems are widely used to introduce precise mutations, such as knocking in/out at targeted genomic sites. Herein, we successfully disrupted the transcription of multiple genes in Bacillus pumilus LG3145 using a series of unspecific guide RNAs (gRNAs) and UgRNA:Cas9 system-assisted cre-box editing. The bases used as gRNAs shared 30-70% similarity with a consensus sequence, a cis-acting element (cre-box) mediating carbon catabolite repression (CCR) of many genes in Bacillus. This triggers trans-crRNA:Cas9 complex wobble cleavage up/downstream of cre sites in the promoters of multiple genes (up to 7), as confirmed by Sanger sequencing and next-generation sequencing (NGS). LG3145 displayed an obvious CCR release phenotype, including numerous secondary metabolites released into the culture broth, ∼ 1.67 g/L white flocculent protein, pigment overflow causing orange-coloured broth (absorbance = 309 nm), polysaccharide capsules appearing outside cells, improved sugar tolerance, and a two-fold increase in cell density. We assessed the relationship between carbon catabolite pathways and phenotype changes caused by unspecific UgRNA-directed cre site wobble editing. We propose a novel strategy for editing consensus targets at operator sequences that mediates transcriptional regulation in bacteria.

Etiology of Severe Pneumonia in Children in Alveolar Lavage Fluid Using a High-Throughput Gene Targeted Amplicon Sequencing Assay.

Objective: To evaluate the diagnostic value of a high-throughput gene targeted amplicon sequencing (TAS) assay for detecting pathogenic microorganisms in alveolar lavage fluid (ALF) from children with severe community-acquired pneumonia (SCAP). Methods: A retrospective study was performed on 48 frozen ALF samples from 47 severe pneumonia cases admitted to Children's Hospital of Fudan University from January 1, 2019, to March 31, 2019. All samples were tested by a multiplex PCR (Multi-PCR) assay and a TAS assay. The results of the TAS panels were parallel compared with Multi-PCR and Conventional Tests (CT) including culture, direct fluorescent antibody method (DFA), and singleplex polymerase chain reaction (PCR). Results: The proportion of pathogens detection by CT was 81.2% (39/48). The 8 common respiratory viruses including respiratory syncytial virus (RSV), adenovirus (ADV), influenza A virus (FLUA), influenza B virus (FLUB), parainfluenza virus 1-3 (PIV1-3), and human Metapneumovirus (hMPV) were found in 31.2% (15/48) of the 48 samples by DFA. With the criteria of CT results used as "Golden Standard" for determing of TAS results, the proportion of pathogens detection by TAS was 70.8% (34/48). The difference of proportion of pathogens detection between TAS and CT was not statistically significant (p = 0.232). The sensitivity and specificity of TAS for pathogens detection based on CT were 87.1% (95% CI, 71.77-95.18%) and 100.0% (95% CI, 62.88-100%), the positive predictive value (PPV) and negative predictive value (NPV) were 100.0% (95% CI, 87.35-100%) and 64.2% (95% CI, 35.62-86.02%), respectively. While Multi-PCR results were used as "Golden Standard," the total pathogens detection rate of TAS was 83.3% (40/48), which had a significant difference with that of Multi-PCR (p = 0.003). The sensitivity and PPV of TAS compared with Multi-PCR were 83.3% (95% CI, 69.23-92.03%) and 100.0% (95% CI, 89.08-100%), respectively. High rates of co-infection were proved by CT, Multi-PCR, and TAS. Mycoplasma pneumoniae (MP) and ADV were the two most frequently detected pathogens in all three assays. Conclusion: Compared with the CT and Multi-PCR methods, this TAS assay had a good performance in detecting bacteriological and viral pathogens from ALF. More research is needed to establish interpretation criteria based on TAS reads or analysis platforms.

A brain-actuated robotic arm system using non-invasive hybrid brain-computer interface and shared control strategy.

Objective.The electroencephalography (EEG)-based brain-computer interfaces (BCIs) have been used in the control of robotic arms. The performance of non-invasive BCIs may not be satisfactory due to the poor quality of EEG signals, so the shared control strategies were tried as an alternative solution. However, most of the existing shared control methods set the arbitration rules manually, which highly depended on the specific tasks and developer's experience. In this study, we proposed a novel shared control model that automatically optimized the control commands in a dynamical way based on the context in real-time control. Besides, we employed the hybrid BCI to better allocate commands with multiple functions. The system allowed non-invasive BCI users to manipulate a robotic arm moving in a three-dimensional (3D) space and complete a pick-place task of multiple objects.Approach.Taking the scene information obtained by computer vision as a knowledge base, a machine agent was designed to infer the user's intention and generate automatic commands. Based on the inference confidence and user's characteristic, the proposed shared control model fused the machine autonomy and human intention dynamically for robotic arm motion optimization during the online control. In addition, we introduced a hybrid BCI scheme that applied steady-state visual evoked potentials and motor imagery to the divided primary and secondary BCI interfaces to better allocate the BCI resources (e.g. decoding computing power, screen occupation) and realize the multi-dimensional control of the robotic arm.Main results.Eleven subjects participated in the online experiments of picking and placing five objects that scattered at different positions in a 3D workspace. The results showed that most of the subjects could control the robotic arm to complete accurate and robust picking task with an average success rate of approximately 85% under the shared control strategy, while the average success rate of placing task controlled by pure BCI was 50% approximately.Significance.In this paper, we proposed a novel shared controller for motion automatic optimization, together with a hybrid BCI control scheme that allocated paradigms according to the importance of commands to realize multi-dimensional and effective control of a robotic arm. Our study indicated that the shared control strategy with hybrid BCI could greatly improve the performance of the brain-actuated robotic arm system.

Association Between Obstructive Sleep Apnea-Hypopnea Syndrome and Outcomes in Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease.

Background and Aims: Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) occurs in 5-10% of all patients with acute myocardial infarction. Obstructive sleep apnea-hypopnea syndrome (OSAHS) is linked to increased cardiovascular morbidity and mortality, but the relationship of OSAHS and outcomes in patients with MINOCA remains unknown. We aimed to evaluate the association between OSAHS and clinical outcomes in patients with MINOCA. Methods: Between January 2015 and December 2016, we carried out a consecutive cohort study of 583 patients with MINOCA and followed them up for 3 years. An apnea-hypopnea index of ≥ 15 events per hour recorded by polysomnography was defined as the diagnostic criterion for OSAHS. The primary end point was all-cause mortality, and the second end point was major adverse cardiovascular or cerebrovascular events (MACCE), a composite of cardiac death, non-fatal myocardial infarction, heart failure, cardiovascular-related rehospitalization, and stroke. Results: All-cause mortality happened in 69 patients and MACCE occurred in 113 patients during the 3-year follow-up. Kaplan-Meier survival curves indicated the significant relationship of OSAHS with all-cause mortality (log-rank P = 0.012) and MACCE (log-rank P = 0.002). Multivariate Cox regression analysis indicated OSAHS as an independent predictor of all-cause mortality and MACCE [adjusted hazard ratio: 1.706; 95% confidence interval (CI): 1.286-2.423; P = 0.008; and adjusted hazard ratio: 1.733; 95% CI: 1.201-2.389; P < 0.001; respectively], independent of age, sex, cardiovascular risk factors and discharge medications. Conclusions: OSAHS is independently associated with increased risk of all-cause mortality and MACCE in patients with MINOCA. Intervention and treatment should be considered to alleviate OSAHS-associated risk.

Therapeutic Effects of SRT2104 on Lung Injury in Rats with Emphysema via Reduction of Type II Alveolar Epithelial Cell Senescence.

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent and severe diseases worldwide with high societal and health care costs. The pathogenesis of COPD is very complicated, and no curative treatment is available. Cellular senescence promotes the development of COPD. Type II alveolar epithelial cells (AECII) play a momentous role in lung tissue repair and maintenance of alveolar homeostasis. Sirtuin 1 (SIRT1), an antiaging molecule involved in the response to chronic inflammation and oxidative stress, regulates many pathophysiological changes including stress resistance, apoptosis, inflammation, and cellular senescence. This study aimed to investigate whether the pharmacological SIRT1 activator SRT2104 protects against AECII senescence in rats with emphysema. Our findings confirmed that SRT2104 administration reduced the pathological characteristics of emphysema and improved lung function parameters, including pulmonary resistance, pulmonary dynamic compliance, and peak expiratory flow. Moreover, SRT2104 treatment upregulated the expression of surfactant proteins A and C, SIRT1, and forkhead box O 3a (FoxO3a), decreased senescence-associated-ß-galactosidase (SA-ß-gal) activity, increased SIRT1 deacetylase activity, and downregulated the levels of p53 and p21. Therefore, SRT2104 administration protected against AECII senescence in rats with emphysema via SIRT1/FoxO3a and SIRT1/p53 signaling pathways and may provide a novel potential therapeutic strategy for COPD.

Affective reactions differ between Chinese and American healthy young adults: a cross-cultural study using the international affective picture system.

BACKGROUND: Several cross-cultural studies have suggested that emotions are influenced by the cultural background. Emotional reactions to International Affective Picture System (IAPS) images were compared between Chinese and American young adults. METHODS: 120 Chinese undergraduates (53 females, 67 males; aged 18-25 years) were enrolled at Zhejiang University, China, and the valence and arousal components of their emotional responses to IAPS images were rated using the Self-Assessment Manikin (SAM) system. Then, valence and arousal scores were compared to those of 100 American undergraduates (50 females, 50 males) of the same age group, enrolled at Florida University and surveyed by Prof. PJ Lang in 2001. RESULTS: Valence scores assigned to 259/816 (31.74%) pictures differed significantly between Chinese and American female participants, while those assigned to 165/816 (20.22%) pictures differed significantly between Chinese and American males (P < 6 × 10(-5)). Of the 816 pictures, the arousal scores assigned to 101/816 (12.38%) pictures differed significantly between Chinese and American female participants; these scores significantly differed in 130/816 (15.93%) pictures between Chinese and American males (P < 6 × 10(-5)). Valence scores for pictures in the Erotic category differed significantly between Chinese and American females (P < 6 × 10(-5)). There were no significant differences in valence scores for the remaining eight categories studied between participants from the two countries, whether female or male. CONCLUSIONS: The IAPS norms require a modification for their appropriate application in Asian cultures.

Phenylbutyric acid inhibits epithelial-mesenchymal transition during bleomycin-induced lung fibrosis.

A recent report showed that unfolded protein response (UPR) signaling was activated during bleomycin (BLM)-induced pulmonary fibrosis. Phenylbutyric acid (PBA) is an endoplasmic reticulum (ER) chemical chaperone that inhibits the UPR signaling. The present study investigated the effects of PBA on BLM-induced epithelial-mesenchymal transition (EMT) and pulmonary fibrosis. For induction of pulmonary fibrosis, all mice except controls were intratracheally injected with a single dose of BLM (3.0mg/kg). In PBA+BLM group, mice were intraperitoneally injected with PBA (150mg/kg) daily. Three weeks after BLM injection, EMT was measured and pulmonary fibrosis was evaluated. BLM-induced pulmonary UPR activation was inhibited by PBA. Moreover, BLM-induced pulmonary nuclear factor kappa B (NF-κB) p65 activation was blocked by PBA. In addition, BLM-induced up-regulation of pulmonary inflammatory cytokines was repressed by PBA. Further analysis showed that BLM-induced α-smooth muscle actin (α-SMA), a marker for EMT, was significantly attenuated by PBA. Moreover, BLM-induced pulmonary collagen (Col1α1 and Col1α2) was obviously inhibited by PBA. Importantly, BLM-induced pulmonary fibrosis, as determined using Sirius red staining, was obviously alleviated by PBA. Taken together, these results suggest that PBA alleviates ER stress-mediated EMT in the pathogenesis of BLM-induced pulmonary fibrosis.

Melatonin inhibits endoplasmic reticulum stress and epithelial-mesenchymal transition during bleomycin-induced pulmonary fibrosis in mice.

Several reports indicate that melatonin alleviates bleomycin (BLM)-induced pulmonary fibrosis in rodent animals. Nevertheless, the exact mechanism remains obscure. The present study investigated the effects of melatonin on endoplasmic reticulum (ER) stress and epithelial-mesenchymal transition (EMT) during BLM-induced lung fibrosis. For the induction of pulmonary fibrosis, mice were intratracheally injected with a single dose of BLM (5.0 mg/kg). Some mice were intraperitoneally injected with melatonin (5 mg/kg) daily for a period of 3 wk. Twenty-one days after BLM injection, lung fibrosis was evaluated. As expected, melatonin significantly alleviated BLM-induced pulmonary fibrosis, as evidenced by Sirius red staining. Moreover, melatonin significantly attenuated BLM-induced EMT to myofibroblasts, as determined by its repression of α-SMA expression. Further analysis showed that melatonin markedly attenuated BLM-induced GRP78 up-regulation and elevation of the cleaved ATF6 in the lungs. Moreover, melatonin obviously attenuated BLM-induced activation of pulmonary eIF2α, a downstream target of the PERK pathway. Finally, melatonin repressed BLM-induced pulmonary IRE1α phosphorylation. Correspondingly, melatonin inhibited BLM-induced activation of XBP-1 and JNK, two downstream targets of the IRE1 pathway. Taken together, these results suggest that melatonin alleviates ER stress and ER stress-mediated EMT in the process of BLM-induced pulmonary fibrosis.