Temperature-Promoted Giant Unilamellar Vesicle (GUV) Aggregation: A Way of Multicellular Formation.

The evolution of unicellular to multicellular life is considered to be an important step in the origin of life, and it is crucial to study the influence of environmental factors on this process through cell models in the laboratory. In this paper, we used giant unilamellar vesicles (GUVs) as a cell model to investigate the relationship between environmental temperature changes and the evolution of unicellular to multicellular life. The zeta potential of GUVs and the conformation of the headgroup of phospholipid molecules at different temperatures were examined using phase analysis light scattering (PALS) and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), respectively. In addition, the effect of increasing temperature on the aggregation of GUVs was further investigated in ionic solutions, and the possible mechanisms involved were explored. The results showed that increasing temperature reduced the repulsive forces between cells models and promoted their aggregation. This study could effectively contribute to our understanding of the evolution of primitive unicellular to multicellular life.

In situ fabrication of a novel CdS/ZnIn2S4/g-C3N4 ternary heterojunction with enhanced visible-light photocatalytic performance.

In this study, a novel g-C3N4-based ternary heterojunction was rationally designed and constructed by the in situ growth of ZnIn2S4 nanosheets and CdS nanoparticles onto the g-C3N4 nanosheets using a facile two-step oil-bath method. Through optimizing the proportion of ZnIn2S4 and CdS component, g-C3N4 nanosheets coupled with ZnIn2S4 nanosheets and CdS nanoparticles (denoted as CdS/ZnIn2S4/g-C3N4) exhibited obviously higher photocatalytic properties for RhB removal than the single-component and dual-component systems. Among the as-obtained ternary photocatalysts, it was found that the ternary CdS/ZnIn2S4/g-C3N4-0.2 photocatalyst displayed the optimum photocatalytic property (96%) within a short time (30 min), which was almost 27.42 and 1.17 times higher than that of pure g-C3N4 and binary ZnIn2S4/g-C3N4-0.7 composite. The excellent activity of the ternary CdS/ZnIn2S4/g-C3N4 heterostructure is assigned to the synergetic effects of CdS nanoparticles, ZnIn2S4 nanosheets and g-C3N4 nanosheets, which not only broaden the visible-light absorption range, but also improve the charge mobility and separation rate, thus boosting the visible-light-driven photocatalytic property of g-C3N4.

Clinical effectiveness and potential predictability of omalizumab in patients with difficult-to-treat chronic rhinosinusitis with nasal polyps and asthma based on the noninvasive markers - A real-life prospective study.

Background: Clinical studies on the effectiveness of omalizumab in patients with difficult-to-treat chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma are scarce in China. Moreover, identifying potential biomarkers predicting its efficacy remains a great challenge. Methods: In this prospective trial, all enrolled patients underwent endoscopic examination, computed tomography, blood tests, etc, and they completed a 22-item sino-nasal outcome test (SNOT-22), visual analogue scale (VAS), and asthma control test (ACT) evaluation, at baseline and after 24-week omalizumab therapy. Results: Twenty-two patients were finally recruited. Their VAS scores were significantly better including nasal congestion, anterior rhinorrhea, postnasal drip, and loss of smell (P < 0.01). Seventeen patients reported a reduction in SNOT-22 scores of ≥8.9 and 19 patients achieved ACT scores >20. The median change in the Lund-MacKay score (LMS) was 6. Both the Lund-Kennedy score (LKS) and nasal polyp score showed significant improvement (P < 0.01). Only 3 parameters in the pulmonary function test showed evident amelioration (P < 0.05). The eosinophilic CRSwNP and the male subgroups showed better improvements in subjective and objective evaluation. A receiver operating characteristic curve indicated a cutoff value of 17.5 and 16.5 in LMS had the moderate predictive value (AUC = 0.706) for the decline in the SNOT-22 (more than 8.9 points) and reduction in anterior rhinorrhea VAS (more than 2 cm), respectively. A cutoff value of 18.5 in ACT could provide the moderate predictive value (AUC = 0.771) for the reduction of loss of smell VAS (more than 2 cm). Conclusions: The beneficial effectiveness of omalizumab in the patients with difficult-to-treat CRSwNP and asthma was confirmed. ECRSwNP and male patients were more likely to have positive responses. The multiple cutoff values for the LMS and ACT may serve as useful predictors for improvement acceptable to difficult-to-treat CRSwNP patients.

Association Between Arterial Blood Gas Variation and Intraocular Pressure in Healthy Subjects Exposed to Acute Short-Term Hypobaric Hypoxia.

PURPOSE: To investigate the association between changes in arterial blood gases and intraocular pressure (IOP) after acute, short-term exposure to simulated elevation of 4000 m above sea level. METHODS: Twenty-five healthy young lowlanders participated in this prospective study. IOP was measured in both eyes with an Accupen tonometer. Arterial blood gas parameters (partial oxygen pressure [PaO2], partial carbon dioxide pressure [PaCO2], pH, and bicarbonate ion [HCO3 -]) were checked using a blood gas analyzer. Measurements were taken at sea level (T1), at 15-minute (T2) and at 2-hour (T3) exposure times to simulated 4000 m above sea level in a hypobaric chamber, and upon return to sea level (T4). Associations between arterial blood gas parameters and IOP were evaluated using multivariate linear regression. RESULTS: PaO2 significantly decreased at T2 and T3, resolving at T4 (P < 0.001). pH significantly increased at T2 and returned to baseline at T3 (P = 0.004). Actual and standard bicarbonate ion both dropped with IOP at T3 and T4. IOP significantly decreased from 16.4 ± 3.4 mm Hg at T1 to 15.1 ± 2.1 mm Hg (P = 0.041) at T3 and remained lower (14.9 ± 2.4 mm Hg; P = 0.029) at T4. IOP was not correlated with pH. Multivariate linear regression showed that lower IOP was associated with lower standard bicarbonate ion (beta = -1.061; 95% confidence interval, -0.049 to -2.074; P = 0.04) when adjusted for actual bicarbonate and diastolic blood pressure. CONCLUSIONS: Hypobaric hypoxia triggers plasma bicarbonate ion reduction which, rather than pH, may decrease aqueous humor formation and subsequently cause IOP reduction. These findings may shed light on the mechanism of IOP regulation at high altitude. TRANSLATIONAL RELEVANCE: Hypoxia-triggered reduction in plasma bicarbonate ion may decrease aqueous humor production, leading to IOP reduction at high altitude. These findings may provide new insight into a potential mechanism of IOP regulation. Hypobaric hypoxia at high altitude is an environmental factor that can reduce IOP and, therefore, deserves further study.

Exhaled Hydrogen Sulfide Predicts Airway Inflammation Phenotype in COPD.

BACKGROUND: The role of exhaled H2S as a marker of airway inflammation and its relationship with COPD severity remain to be determined. METHODS: Airway inflammation was classified in 77 COPD subjects based on the presence of inflammatory cells in induced sputum. We investigated the association between disease phenotype and exhaled H2S, lung function, and plasma levels of several inflammatory factors, including tumor necrosis factor alpha, interleukin-8, and leukotriene B4. RESULTS: In total, 33.77% of enrolled COPD subjects were diagnosed with eosinophilia. These subjects had a longer disease course, smoked fewer cigarettes, and experienced more frequent exacerbation events before study enrollment. However, they also had worse lung function and larger residual volume, they demonstrated greater changes in FEV1 following bronchodilator inhalation. Although levels of plasma inflammatory factors did not significantly differ between subjects with and without eosinophilia, subjects without eosinophilia had significantly higher levels of exhaled H2S (9.19±2.74 vs 7.24±1.68 parts per billion, P=.01). Furthermore, exhaled H2S levels were negatively correlated with induced sputum eosinophils (r=-0.45, P=.05), and positively correlated with inspiratory capacity in COPD subjects (r=0.51, P=.026), but did not correlate significantly with plasma inflammatory factors. A cut-off value of 7.10 parts per billion of exhaled H2S predicted a non-eosinophilic phenotype with 68.6% sensitivity and 77.9% specificity. CONCLUSIONS: Exhaled levels of H2S were lower in subjects with eosinophilia. Increased levels of exhaled H2S predicted a non-eosinophilic phenotype in our study population.

Correlation between levels of exhaled hydrogen sulfide and airway inflammatory phenotype in patients with chronic persistent asthma.

BACKGROUND AND OBJECTIVE: Endogenous hydrogen sulfide (H2 S) may be a biomarker of asthma severity and activity. However, the relationship between exhaled H2 S and airway inflammation phenotypes in asthma remains unclear. This study examined associations between endogenous H2 S and chronic airway inflammatory phenotypes in patients with chronic persistent asthma. METHODS: One hundred forty-eight patients (47 males, 101 females, 47.4 ± 15.3 years old) with chronic persistent asthma were enrolled. Induced sputum cells were examined, and patients were grouped according to sputum inflammatory cell composition. Baseline demographics, Asthma Control Test (ACT) scores, spirometry data and H2S levels in exhaled air and plasma were obtained for all patients. RESULTS: The eosinophilic, neutrophilic, mixed granulocytic and paucigranulocytic inflammation groups included 57 (38.5%), 28 (18.9%), 23 (15.5%) and 40 (27%) subjects, respectively. The paucigranulocytic group had the best lung function, and patients with eosinophilic inflammation had lower ACT scores than patients with paucigranulocytic findings. In the eosinophilic group, lower exhaled H2S were found and exhaled H2 S levels were negatively correlated with sputum eosinophil counts (R = -0.428, P < 0.01). Exhaled H2 S levels were positively correlated with percent of predicted forced expiratory volume in 1 s (R = 0.567, P < 0.01) and ACT score (R = 0.519, P < 0.01). CONCLUSIONS: Exhaled H2 S may be a useful marker of airway inflammation in asthma.

Exhaled hydrogen sulfide in patients with chronic obstructive pulmonary disease and its correlation with exhaled nitric oxide.

BACKGROUND: Exhaled nitric oxide (NO) is a noninvasive biomarker of airway inflammation in pulmonary diseases. Hydrogen sulfide (H2S), as the third member of the gasotransmitter family, is involved in the pathophysiological process in lung diseases. H2S also exists in exhaled breath and can be sampled non-invasively. The study investigated the level of exhaled H2S in patients with chronic obstructive pulmonary disease (COPD) and its correlation with exhaled NO. METHODS: Levels of exhaled NO and H2S, lung function, and cell differential counts in induced sputum were studied in 19 patients with acute exacerbation of COPD (AECOPD), 19 patients with stable COPD and seven healthy smoke controls. RESULTS: Exhaled H2S levels were similar in patients with AECOPD (10.0 parts per billion (ppb), 8.0-13.0 ppb), stable COPD (10.0 ppb, 9.0-12.0 ppb), and healthy controls (9.0 ppb, 8.0-16.0 ppb) (P > 0.05). Exhaled NO levels were similar in patients with AECOPD (155.0 ppb, 129.0-190.0 ppb), stable COPD (154.0 ppb, 133.0-175.0 ppb) and healthy controls (165.0 ppb, 112.0-188.0 ppb) (P > 0.05). Exhaled H2S levels correlated positively with exhaled NO in all healthy controls and patients with COPD (r=0.467, P < 0.01). No significant correlation was found between the exhaled H2S level and percentage of predicted FEV1 (P > 0.05) and proportion of different cell types in induced sputum (P > 0.05). CONCLUSIONS: There is a correlation between exhaled H2S and exhaled NO. The role of exhaled H2S in airway inflammation in COPD still needs further investigation.

Involvement of endogenous hydrogen sulfide in cigarette smoke-induced changes in airway responsiveness and inflammation of rat lung.

Hydrogen sulfide (H2S), recently considered the third endogenous gaseous transmitter, may have an important role in systemic inflammation. We investigated whether endogenous H2S may be a crucial mediator in airway responsiveness and airway inflammation in a rat model of chronic exposure to cigarette smoke (CS). Rats randomly divided into control and CS-exposed groups were treated with or without sodium hydrosulfide (NaHS, donor of H2S) or propargylglycine (PPG, inhibitor of cystathionine-γ-lyase [CSE], an H2S-synthesizing enzyme) for 4-month exposure. Serum H2S level and CSE protein expression in lung tissue were higher, by 2.04- and 2.33-fold, respectively, in CS-exposed rats than in controls (P<0.05). Exogenous administration of NaHS to CS-exposed rats alleviated airway reactivity induced by acetylcholine (Ach) or potassium chloride (KCl) by 17.4% and 13.8%, respectively, decreased lung pathology score by 32.7%, inhibited IL-8 and TNF- α concentrations in lung tissue by 34.2% and 31.4%, respectively, as compared with CS-exposed rats (all P<0.05). However, blocking endogenous CSE with PPG in CS-exposed rats increased airway reactivity induced by Ach or KCl, by 24.1% and 24.5%, respectively, and aggravated lung pathology score, by 44.8%, as compared with CS-exposed rats (all P<0.01). Incubation in vitro with NaHS, 1-3 mmol/L, relaxed rat tracheal smooth muscle precontracted by Ach or KCl. However, the NaHS-induced relaxation was not blocked by glibenclamide (10⁻4 mol/L), L-NAME (10⁻4 mol/L), or ODQ (1 µmol/L) or denudation of epithelium. Endogenous H2S may have a protective role of anti-inflammation and bronchodilation in chronic CS-induced pulmonary injury.

Economic analysis in admitted patients with acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: The socio-economic burden of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing is not fully understood. The study investigated the hospitalization cost in patients with AECOPD and the associated factors. METHODS: A multi-center, retrospective study was conducted in the four hospitals in Beijing including two level III hospitals and two level II hospitals. Patients with AECOPD admitted to the hospitals between January and December in 2006 were enrolled. The hospitalization cost and its relationship with disease severity and treatment were analyzed. RESULTS: Totally 439 patients were enrolled with 294 men (67.0%) and a mean age 73.4 years. The mean hospital stay was 20.7 days. A total of 204 patients (46.5%) had respiratory failure, 153 (34.9%) with cor pulmonale, 123 (28.0%) with coronary artery disease, 231 (52.6%) with hypertension, 70 (15.9%) with cerebrovascular disease and 32 (7.3%) with renal failure. The percentage of drug cost to total cost was the highest (71.2%), followed by laboratory cost (16.7%), therapy cost (9.7%), oxygen cost (7.3%), radiology cost (4.5%), examination cost (4.5%), bed cost (4.1%). Correlation analysis showed that cost was positively correlated with age, hospitalization days, co-morbidities such as respiratory failure and cor pulmonale, hypertension. Three hundred and twenty-one patients were further analyzed. The hospitalization cost increased in patients with non-invasive ventilation (P < 0.01), invasive mechanical ventilation (P < 0.01), ICU stay (P < 0.01), antibiotics (P < 0.05), systemic steroids (P < 0.01), and poor prognosis (P < 0.05). Correlation analysis showed that the hospitalization cost was negatively correlated with percentage forced expiratory volume in 1 second (FEV(1)%) (r = -0.149, P < 0.05), pH (r = -0.258, P < 0.01), and PaO(2) (r = -0.131, P < 0.05), positively correlated with PaCO2 (r = 0.319, P < 0.01), non-invasive positive pressure ventilation (r = 0.375, P < 0.01) and duration (r = 0.463, P < 0.01), invasive mechanical ventilation (r = 0.416, P < 0.01) and duration (r = 0.511, P < 0.01), ICU stay (r = 0.390, P < 0.01) and duration (r = 0.650, P < 0.01), antibiotics (r = 0.140, P < 0.05) and systemic steroids (r = 0.202, P < 0.01). CONCLUSIONS: AECOPD had a great impact on healthcare resources utilization. Disease severity, use of non-invasive or invasive ventilation, ICU stay and usage of antibiotics and systemic steroids were the major determinants of hospitalization cost. Long-term regular treatment aimed at reducing the frequency of acute exacerbation will lower the social and economic burden of chronic obstructive pulmonary disease (COPD).