Tiotropium in Early-Stage Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with mild or moderate chronic obstructive pulmonary disease (COPD) rarely receive medications, because they have few symptoms. We hypothesized that long-term use of tiotropium would improve lung function and ameliorate the decline in lung function in patients with mild or moderate COPD. METHODS: In a multicenter, randomized, double-blind, placebo-controlled trial that was conducted in China, we randomly assigned 841 patients with COPD of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1 (mild) or 2 (moderate) severity to receive a once-daily inhaled dose (18 µg) of tiotropium (419 patients) or matching placebo (422) for 2 years. The primary end point was the between-group difference in the change from baseline to 24 months in the forced expiratory volume in 1 second (FEV1) before bronchodilator use. Secondary end points included the between-group difference in the change from baseline to 24 months in the FEV1 after bronchodilator use and the between-group difference in the annual decline in the FEV1 before and after bronchodilator use from day 30 to month 24. RESULTS: Of 841 patients who underwent randomization, 388 patients in the tiotropium group and 383 in the placebo group were included in the full analysis set. The FEV1 in patients who received tiotropium was higher than in those who received placebo throughout the trial (ranges of mean differences, 127 to 169 ml before bronchodilator use and 71 to 133 ml after bronchodilator use; P<0.001 for all comparisons). There was no significant amelioration of the mean (±SE) annual decline in the FEV1 before bronchodilator use: the decline was 38±6 ml per year in the tiotropium group and 53±6 ml per year in the placebo group (difference, 15 ml per year; 95% confidence interval [CI], -1 to 31; P=0.06). In contrast, the annual decline in the FEV1 after bronchodilator use was significantly less in the tiotropium group than in the placebo group (29±5 ml per year vs. 51±6 ml per year; difference, 22 ml per year [95% CI, 6 to 37]; P=0.006). The incidence of adverse events was generally similar in the two groups. CONCLUSIONS: Tiotropium resulted in a higher FEV1 than placebo at 24 months and ameliorated the annual decline in the FEV1 after bronchodilator use in patients with COPD of GOLD stage 1 or 2. (Funded by Boehringer Ingelheim and others; Tie-COPD ClinicalTrials.gov number, NCT01455129 .).

Cigarette smoke upregulates SPRR3 by favoring c-Jun/Fra1 heterodimerization in human bronchial epithelial cells.

AIM: The airway epithelium of smokers exhibits upregulated SPRR3, an indicator of pathogenic keratinization. The mechanisms underlying this phenomenon require investigation. PATIENTS & METHODS: Human bronchial epithelial (HBE) SPRR3 expression was analyzed by smoking status. Primary HBE cells were exposed to cigarette smoke (CS). SPRR3 expression, SPRR3 promoter activity, AP-1 factor binding and AP-1 factors' effects were analyzed. RESULTS: Current smokers display SPRR3 upregulation relative to never smokers. CS upregulates SPRR3 transcription in an exposure-dependent manner. CS promotes c-Jun and Fra1 binding to the SPRR3-AP-1/TRE site. Wild-type c-Jun and Fra1 upregulate, whereas c-Jun and Fra1, dominant-negative mutants, suppress SPRR3 promoter activity. CONCLUSION: CS induces SPRR3 upregulation in HBE cells by promoting aberrant c-Jun/Fra1 dimerization.

Serum growth differentiation factor 15 as a biomarker for malnutrition in patients with acute exacerbation of chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease that often coexists with malnutrition during acute exacerbation (AECOPD) and significantly affects the prognosis. Previous studies have shown that growth differentiation factor 15 (GDF15) levels promote appetite suppression, weight loss, and muscle weakness, and are markedly high in peripheral blood following inflammatory stimulation. However, it is still unknown whether serum GDF15 levels can be used to predict malnutrition in patients with AECOPD. Methods: A total of 142 patients admitted to the Department of Respiratory Medicine at Anshun People's Hospital between December 2022 and August 2023 were selected for this study. The participants were divided into two groups: malnutrition group (n = 44) and non-malnutrition group (n = 98) based on a body mass index (BMI) < 18.5 kg/m2, according to the Global Leadership Initiative on Malnutrition (GLIM) criteria. Serum GDF15 levels were measured using the enzyme-linked immunosorbent assay (ELISA) and compared between the two groups. Spearman correlation analysis was used to examine the association between serum GDF15 levels, baseline data, and clinical indicators. Binary logistic regression was used to identify the independent risk factors for AECOPD combined with malnutrition. The predictive value of serum GDF15, albumin (ALB), and a combination of these was evaluated to identify malnutrition in patients with AECOPD using a receiver operating characteristic (ROC) curve. Results: Serum GDF15 levels in patients with malnutrition and AECOPD were significantly higher than those in patients without malnutrition, whereas the serum ALB levels were significantly lower than those in patients without malnutrition (p < 0.001). Moreover, serum GDF15 levels were negatively correlated with BMI (r = -0.562, p < 0.001), mid-arm circumference (r = -0.505, p < 0.001), calf circumference (r = -0.490, p < 0.001), total protein (r = -0.486, p < 0.001), ALB (r = -0.445, p < 0.001), and prognostic nutritional index (r = -0.276, p = 0.001), and positively correlated with C-reactive protein (r = 0.318, p < 0.001), COPD assessment test score (r = 0.286, p = 0.001), modified medical research council classification (r = 0.310, p < 0.001), and global initiative for chronic obstructive pulmonary disease grade (r = 0.177, p = 0.035). Furthermore, serum GDF15 levels were an independent risk factor for malnutrition in patients with AECOPD (OR = 1.010, 95% CI, 1.003∼1.016). The optimal cut-off value of serum GDF15 level was 1,092.885 pg/mL, with a sensitivity of 65.90% and a specificity of 89.80%, while the serum ALB level was 36.15 g/L, with a sensitivity of 86.40% and a specificity of 65.00%, as well as a combined sensitivity of 84.10% and a specificity of 73.90%. Serum GDF15 and serum ALB levels had a good predictive ability (AUC = 0.856, AUC = 0.887), and the ROC revealed a greater combined prediction value for the two (AUC = 0.935). Conclusion: Serum GDF15 levels could be used as a potential biomarker in the prediction of malnutrition in patients with AECOPD, offering a guidance for future clinical evaluation of malnutrition.

Palladium Nanoclusters Confined in MOF@COP as a Novel Nanoreactor for Catalytic Hydrogenation.

Metal-nanocluster-doped porous materials are attracting considerable research attention due to their specific catalytic performance. In this study, core-shell metal-organic frameworks@covalent organic polymer (MOF@COP) nanocomposites were formed by the covalent linking of chemically stable COP on the surface of size-selective UiO-66-NH2. Pd nanoclusters with an average diameter of ∼0.8 nm were successfully confined in UiO-66-NH2@COP, and the obtained nanoreactor, referred to as UiO-66-NH2@COP@Pd, exhibited abundant porosity, high stability, and large surface area. Notably, the UiO-66-NH2@COP@Pd nanoreactor exhibited superior catalytic activity and stability for the catalytic reduction of 4-nitrophenol and hydrogenation of other nitroarenes, demonstrating the potential of Pd-cluster-doped MOF@COP hybrid materials as candidates for efficient catalytic hydrogenation. This study may provide new avenues for the construction of MOF@COP-hybrid-material-based heterogeneous catalysts for efficient catalytic applications.

Numerical studies of a low-loss and broad-pass-band single-sided-structure left-handed metamaterial.

A single-sided structure left-handed metamaterial (LHM), of which the symmetric paired split-ring resonators are connected directly through cut wires, is discussed in this paper. This connected single-sided LHM can exhibit a low loss and broad negative refraction passband. Good agreement of the retrieved result and the simulated result verify the above conclusion by comparison with the in-plane case and the off-plane case [T. Koschny, M. Kafesaki, E. N. Economou, and C. M. Soukoulis, Phys. Rev. Lett. 93, 107402 (2004)].

Simultaneous normal and parallel incidence planar left-handed metamaterial.

We investigate numerically the negative refraction of a simultaneous normal and parallel incidence planar left-handed metamaterial (LHM) in this paper. This LHM is comprised of fourfold C-shaped rings, which are printed on both sides of the substrates symmetrically, and it can exhibit left-handed properties with electromagnetic wave incident in three different directions. The retrieved result and the simulated result verify the left-handed properties of the fourfold C-shaped metamaterial very well. Then the different electric responses of the normal and parallel incidence cases to the incident electromagnetic wave are discussed, and it is due to the different distribution of the induced currents in the metallic wires.

Ru nanoclusters confined in porous organic cages for catalytic hydrolysis of ammonia borane and tandem hydrogenation reaction.

The fabrication of narrow-sized metal nanoclusters for heterogeneous catalysis has attracted widespread research attention. Nevertheless, it is still a significant challenge to fabricate highly dispersed metal-nanocluster-based catalysts with high activity and stability. In this study, 1,3,5-benzenetricarboxylate and 1,2-diaminocyclohexane were used as precursors to fabricate porous organic cages (POCs), CC3-R. CC3-R exhibited a high specific surface area and a microporous-mesoporous structure. In addition, ultrafine Ru nanoclusters were successfully encapsulated in CC3-R with high dispersion via impregnation and subsequent reduction, affording Ru nanoclusters with a precisely controlled size of ∼0.65 nm. As-obtained Ru(1.45%)@CC3-R exhibited significantly enhanced catalytic activities toward the hydrolysis of ammonia borane (AB) and exhibited high conversion and selectivity for the tandem hydrogenation of nitroarenes and hydrogenation of quinoline in water under mild conditions. In addition, the Ru(1.45%)@CC3-R catalyst exhibited high stability and good recyclability. This study should provide a novel strategy for fabricating highly dispersed ultrafine nanocluster-based catalysts for various catalysis applications.

Ultra-fine Pd nanoparticles confined in a porous organic polymer: A leaching-and-aggregation-resistant catalyst for the efficient reduction of nitroarenes by NaBH4.

Porous organic polymers (POPs) containing nitrogenous substituents have potential practical applications as heterogeneous catalysts based upon controlled porous structure and surface-anchored noble metal nanoparticles (NMNPs). In this work we prepared a POP material from piperazine and cyanuric chloride starting materials (PC-POP). The PC-POP material contains numerous triazinyl moieties, thus rendering the pores hydrophobic. Subsequently, by means of a novel reverse double-solvent approach (RDSA), microdroplets of Pd(AcO)2/CH2Cl2 were introduced into the hydrophobic pores of PC-POP in an aqueous environment; Pd(II) was rapidly reduced by NaBH4 to form ultra-fine Pd NPs and confined within the pores of PC-POP at high dispersity. The extensive porosity and dispersity of the Pd NPs made the active sites readily accessible, and led to efficient mass transfer. Thus, Pd@PC-POP exhibits superior catalytic performance in catalytic reduction of various nitroarenes. Furthermore, Pd@PC-POP has excellent recyclability, without significant loss of activity nor leaching of Pd active sites during 10 successive reaction cycles. This work points to a practical and cost-effective approach to preparation of POP materials, and also for confining ultra-fine NMNPs in POPs for use as catalysts.

Biomass Sucrose-Derived Cobalt@Nitrogen-Doped Carbon for Catalytic Transfer Hydrogenation of Nitroarenes with Formic Acid.

Fabrication of non-noble metal-based heterogeneous catalysts by a facile and cost-effective strategy for ecofriendly catalytic transfer hydrogenation (CTH) is of great significance for organic transformations. A cobalt@nitrogen-doped carbon (Co@NC) catalyst was prepared from renewable biomass-derived sucrose, harmless melamine, and earth-abundant Co(AcO)2 as the precursor materials by hydrothermal treatment and carbonization. Co nanoparticles (NPs) were coated with NC shells and uniformly embedded in the NC framework. The as-obtained Co@NC-600 (carbonized at 600 °C) catalyst exhibited excellent catalytic efficiency for CTH of various functionalized nitroarenes with formic acid (FA) as hydrogen donor in aqueous solution. The uniformly incorporated N atoms in the C matrix and the encapsulated Co NPs showed synergistic effects in the CTH reactions. A mechanistic analysis indicated that the protons from FA were activated by Co sites after being captured by N atoms, and then reacted with nitroarenes adsorbed on the surface of the catalysts to generate the corresponding aromatic amines. Moreover, the catalyst showed excellent durability and reusability without obvious decrease in activity even after five reaction cycles. Thus, the study reported herein provides a cost-effective, sustainable strategy for fabrication of biomass-derived non-noble metal-based catalysts for green and efficient catalytic transformations.

Carboplatin-induced hematotoxicity among patients with non-small cell lung cancer: Analysis on clinical adverse events and drug-gene interactions.

In order to clarify the risk of hematotoxicity of carboplatin, we inspected 19901 case reports of non-small cell lung cancer patients that were submitted to the FDA Adverse Event Reporting System (FAERS) between January 2004 and December 2015. These comprised 3907 cases which were treated with carboplatin and 15994 cases which were treated with other therapies in the absence of carboplatin. By comparison, carboplatin cases were significantly more likely to report anemia (OR = 2.27, 95% CI 1.85-2.78, P = 5.04×10-15), neutropenia (OR = 2.27, 95% CI 1.76-2.92, P = 2.39×10-10), and thrombocytopenia (OR = 2.38, 95% CI 1.84-3.08, P = 5.60×10-11). We further explored published evidences and found 205 human genes interacting with carboplatin. Functional analysis corroborated that these genes were significantly enriched in the biochemical pathway of hematopoietic cell lineage (adjusted P = 6.02×10-11). This indicated that carboplatin could profoundly affect the development of blood cells. Given the early awareness of the hematologic risks, great caution should be exercised in prescribing carboplatin to non-small cell lung cancer patients. And functional enrichment analysis on carboplatin-related genes warranted subsequent research with regard to the underlying toxicological mechanisms.

Water vapor diffusion effects on gas dynamics in a sonoluminescing bubble.

Calculations based on a consideration of gas diffusion of gas dynamics in a sonoluminescing bubble filled with a noble gas and water vapor are carried out. Xenon-, argon-, and helium-filled bubbles are studied. In the absence of shock waves, bubble temperatures are found to be decreased, a decrease attributable to the large heat capacity of water vapor. Peak bubble temperature reductions are seen in bubbles containing Xe or Ar but not in those containing He. Further extrapolations provide evidence for the occurrence of shock waves in bubbles with Xe and water vapor. No shock waves are observed in bubbles with Ar or He.