Lycium barbarum polysaccharides attenuate nonylphenol and octylphenol-induced oxidative stress and neurotransmitter disorders in PC-12 cells.

Nonylphenol (NP) and octylphenol (OP) are environmental contaminants with potential endocrine disrupting effects. However, there is limited research on the mechanisms and intervention of combined NP and OP exposure-induced neurotoxicity. This study aims to explore the cytotoxicity of combined NP and OP exposure and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. In present study, LBP (62.5, 125 and 250 µg/mL) were applied to intervene rat adrenal pheochromocytoma (PC-12) cells treated with combined NP and OP (NP: OP = 4:1, w/w; 1, 2, 4 and 8 µg/mL). The results showed that NP and OP induced oxidative stress, disrupted the 5-hydroxytryptamine (5-HT) and cholinergic systems in PC-12 cells. Additionally, they activated the p38 protein kinase (p38) and suppressed the expression of silent information regulation type 1 (SIRT1), monoamine oxidase A (MAOA), phosphorylated cyclic-AMP response binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin-related kinase receptor type B (p-TrkB). However, N-acetyl-L-cysteine (NAC) treatment counteracted the changes of signalling molecule p38, SIRT1/MAOA and CREB/BDNF/TrkB pathways-related proteins induced by NP and OP. LBP pretreatment ameliorated combined NP and OP exposure-induced oxidative stress and neurotransmitter imbalances. Furthermore, the application of LBP and administration of a p38 inhibitor both reversed the alterations in the signaling molecule p38, as well as the proteins associated to the SIRT1/MAOA and CREB/BDNF/TrkB pathways. These results implied that LBP may have neuroprotective effects via p38-mediated SIRT1/MAOA and CREB/BDNF/TrkB pathways.

Lycium barbarum polysaccharides attenuate oxidative stress and mitochondrial toxicity induced by mixed plasticizers in HepG2 cells through activation of Nrf2.

AIMS: In daily life, it is common for humans to be exposed to multiple phthalate esters (PAEs). However, there is limited research on the mechanisms and intervention of combined PAEs toxicity. This study aims to explore the cytotoxicity of combined PAEs and evaluate the potential of Lycium barbarum polysaccharides (LBP) in mitigating the aforementioned toxicity. MAIN METHODS: LBP (62.5, 125 and 250 µg/mL) were applied to intervene HepG2 cells treated with DEHP and DBP mixtures (50, 100, 200, 400 and 800 µg/mL). Western Blot and different kits were mainly performed in our study. KEY FINDINGS: DEHP and DBP mixtures suppressed the expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and activated MAPK pathway by increasing ROS. Combined DEHP and DBP exposure reduced ATP content and inhibited the mitochondrial biogenesis pathway in HepG2 cells through oxidative stress, which in turn caused cytotoxicity. LBP reduced oxidative stress and cell death induced by mixed plasticizers, upregulated Nrf2 levels and mitochondrial biogenesis pathway levels and inhibited MAPK pathway activation. Notably, after treating HepG2 cells with Nrf2-specific inhibitor (ML385, 0.5 µM), we found that the activation of Nrf2 played a crucial role on LBP intervention of DEHP and DBP induced HepG2 cytotoxicity. SIGNIFICANCE: This study not only enhances our understanding of the toxicological effects caused by combined PAEs exposure, but also has significant implications in devising strategies to mitigate the toxicological consequences of combined exposure to exogenous chemicals through the investigation of the role of LBP.

Spatial coupling relationship between older adults and elderly care resources in the Yangtze River Delta.

The imbalance between supply and demand of elderly care resources in the Yangtze River Delta is increasing. By the older adult agglomeration, spatial cluster analysis, hotspot analysis, and coupling coordination model, this study explores the spatial coupling relationship between older adults and elderly care resources in the Yangtze River Delta in 2020 from the perspective of a supply-and-demand balance. The results demonstrate that: (1) population aging is mainly in the moderate aging stage, followed by the primary aging stage; (2) there are significant spatial differences in elderly care resources on the urban scale in the Yangtze River Delta; and (3) elderly care resources and the older adults in the Yangtze River Delta are mostly highly coupled. However, Nantong, with the highest degree of aging, has a serious mismatch in life service resources and ecological environment resources. The social security resources and medical resources of provincial capital cities with low aging are mismatched. Medical and health resources in underdeveloped areas are seriously mismatched. The social security resources are barely matched in Shanghai. A path for optimizing the spatial allocation of elderly care resources is proposed. This research offers a decision-making reference for coordinating elderly care resources distribution.

COF-300-AR@CRL as a two-in-one nanocatalyst for one-step chemiluminescent detection of diphenyl ether herbicide residues in vegetable and fruit samples.

A sensitive and accurate chemiluminescence (CL) method was developed for one-step determination of diphenyl ether herbicides at trace level with nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether) as a model analyte. Candida rugosa lipase (CRL) was immobilized on a nanocarrier of amine-linked covalent organic framework (named as COF-300-AR) through a self-assembly strategy. The formed nanocomposite of COF-300-AR@CRL owns dual enzymatic catalytic activities. It can directly catalyze luminol-dissolved oxygen reaction to produce an intense CL emission by virtue of oxidase mimic activity of COF-300-AR but also effectively decompose nitrofen to release phenolic compounds by the immobilized CRL. The released phenolic compounds own strong reducing capacity and in turn decrease the CL signal sharply. Under the optimal conditions, the decreased CL intensity presents a good linear response to nitrofen concentration in the 0.02-50.0 µM range. The limit of detection (LOD, 3sb/S) is 11 nM and the precision is 2.0% for replicate measurements of 50.0 nM nitrofen solution (n = 11). This method has the advantages of rapid analytical efficiency, good selectivity, satisfactory stability, and recyclability. Recovery experiments were conducted on spiked vegetable and fruit samples with the recoveries falling in the range 90.0-107.0%.

Isolable Tetragold(0) Clusters with Polarity-Tunable exo-Au-Au Bond via Intramolecular σ-Aromatization.

Intramolecular π-aromatization is a trait of many organic compounds that enhances the stability of their structures and polarizes related C-C π bonds. In contrast, rare study is focused on this phenomenon in metal clusters. Many existing homometallic clusters exhibit aromaticity, often characterized by nonpolar metal-metal bonds and a high degree of symmetry. However, synthesizing low-symmetric homometallic clusters with high-polar metal-metal bonds is challenging due to their limited thermodynamic stability. Herein, we report a facile strategy for the synthesis of [Au(µ2 -ER2 )]3 -AuPMe3 (E=Ge, Sn; R2 =1,1,4,4-tetrakis(trimethylsilyl)butane-1,4-diyl) clusters and reveal a novel stabilization mode, intramolecular σ-aromatization. Our electronic structure analyses show that these low-symmetric clusters possess a ten-electron σ-aromatic system, which is achieved via intramolecular σ-aromatization. Moreover, the strength of σ-aromaticity gives rise to a polarity-tunable exo-Au-Au bond.

Graphene supported FeS2 nanoparticles with sandwich structure as a promising anode for High-Rate Potassium-Ion batteries.

Pyrite FeS2 now emerges as a promising anode for potassium-ion batteries (PIBs) due to its low cost and high theoretical capacity. However, the significant volume expansion, low electrical conductivity, and the ambiguous mechanism related to potassium storage severely hinder its development for PIBs anodes. Herein, FeS2 nanostructures are skillfully dispersed on the graphene surface layer by layer (FeS2@C-rGO) to form a sandwich structure by using Fe-based metal organic framework (Fe-MOF) as precursors. The unique structural design can improve the transfer kinetics of K+ and effectively buffer the volume expansion during cycling, thereby enhancing the potassium storage performance. As a result, the FeS2@C-rGO delivers a high capacity of 550 mAh/g at a current density of 0.1 A/g. At a high rate of 2 A/g, the capacity can maintain 171 mAh/g even after 500 cycles. Moreover, the electrochemical reaction mechanism and potassium storage behavior are revealed by in-situ X-ray diffractionand density functional theory calculations. This work not only provides a novel insight into the structural design of electrode materials for high-performance PIBs, but also proposes a valuable understanding of the potassium storage mechanism of the FeS2-based anode.

Compliance and rehabilitation effects of Zheng's supine rehabilitation exercise performed at home among patients with chronic obstructive pulmonary disease: a retrospective study.

Background: Zheng's supine rehabilitation exercise (ZSRE) can be performed by elderly patients with the acute exacerbation of severe or extremely severe chronic obstructive pulmonary disease (COPD) with high safety and compliance and was helpful for their recovery. Investigation is warranted of the compliance and rehabilitation effects of ZSRE performed at home in patients with COPD. Methods: We performed telephone interviews with 157 patients with COPD who were hospitalized on the 26th floor of the National Clinical Research Center for Respiratory Disease and who received COPD education and ZSRE training from 1 September 2015 to 31 August 2016. We retrospectively analyzed the patients' compliance with performing ZSRE at home after discharge and the frequency of hospitalization for treatment of acute exacerbation in both the previous and subsequent years. Results: Among the 157 patients, 66 failed to complete home ZSRE after discharge (non-rehabilitation group), 41 performed home ZSRE once a day after discharge (one-session rehabilitation group), and 50 performed home ZSRE at least twice a day after discharge (multiple-session rehabilitation group). The home ZSRE compliance rate was 57.96% (91/157). There were no significant differences in the mean number of hospitalizations in the year prior to receiving COPD education and ZSRE training among the non-rehabilitation group (1.06±0.75), one-session rehabilitation group (1.27±0.78), and multiple-session rehabilitation group (1.16±0.91). However, there was a significant difference in the mean number of hospitalizations among the groups in the year following discharge (1.44±1.17, 0.78±0.82, and 0.66±0.75, respectively). The number of hospitalizations significantly increased in the non-rehabilitation group and significantly decreased in the one- and multiple-session rehabilitation groups. Conclusions: Home ZSRE can be performed with high compliance by elderly patients with severe or extremely severe COPD and can reduce the number of readmissions.

Trinuclear anionic gold clusters bridged by dialkylsilylene and dialkylgermylene.

While the chemistry of gold clusters has been developed rapidly, the knowledge of trinuclear gold clusters with low-valent gold remains scarce. Herein, we report the synthesis, structural characterization, and density functional theory (DFT) calculations of trinuclear anionic gold clusters 3a and 3b ligated by dialkylsilylene (1a) and dialkylgermylene (1b), respectively.

Structure and reactivity of germylene-bridged digold complexes.

The bonding between gold and main-group metallic elements (M) featuring Auδ--Mδ+ polarity, has been studied recently. The gold in the bonds is expected to have the oxidation number of -1, and hence, nucleophilic. However, the knowledge of the reactivity of the gold-metal bonds remains limited. Here, we report digold-substituted germanes of the form of R'2Ge(AuPR3)(AuGeR'2) (3a; R = Me, 3b; R = Et), featuring two Au-Ge(IV) and one Au-Ge(II) bonds. DFT calculations of 3a revealed the existence of high-lying σ(Ge-Au) type HOMO and low-lying LUMO with germylene pπ nature. A pendular motion of AuPR3 group between Ge(IV) and Ge(II) of 3 occurs in the NMR time scale, suggesting that the Ge(II) center has an enhanced electrophilicity to be attacked by the nucleophilic gold (-I) atom. 3a reacts with nucleophilic Cl- and electrophilic MeOTf reagents at Ge(II) and Ge(IV) centers, respectively.

Chemiluminescence resonance energy transfer determination of uric acid with fluorescent covalent organic framework as energy acceptor.

A simple and feasible strategy was developed for the preparation of fluorescent covalent organic frameworks (COFs) TpPa-1@FL. The TpPa-1-1@FL was prepared via a self-assembly strategy by soaking non-fluorescent COFs TpPa-1 into strong fluorescent fluorescein (FL) solution. A chemiluminescence resonance energy transfer (CRET) system was constructed by the combination strong fluorescent TpPa-1@FL with TCPO-hydrogen peroxide (H2O2) reaction. The chemiluminescence (CL) signal of the system was further improved by the addition of bovine serum albumin (BSA). The CRET system can determine H2O2 with a linear range response from 5.0 µmol/L to 20.0 mmol/L and a detection limit of 1.1 µmol/L. The CRET system was further exploited for indirect detection of uric acid with coupling of uricase. A good linear relationship was obtained for uric acid in the 10.0-400.0 µmol/L concentration range with a detection limit of 3.8 µmol/L. The practicability of this method was assessed by the determination of uric acid in real samples of human serum and urine.

Glucose oxidase@zinc-doped zeolitic imidazolate framework-67 as an effective cascade catalyst for one-step chemiluminescence sensing of glucose.

A chemiluminescence (CL) sensor was constructed for the one-step determination of glucose. Glucose oxidase (GOx) was successfully encapsulated into Zn-doped zeolitic imidazolate framework-67 (Zn-ZIF-67) via a simple one-pot strategy. The as-prepared GOx@Zn-ZIF-67 nanocomposite can trigger cascade reactions of glucose oxidation to generate H2O2 and H2O2-mediated luminol reaction to give an intense CL emission. The sensor responds linearly to glucose in the 20.0-400.0 µmol·L-1 range with a limit of detection (LOD) of 4.7 µmol·L-1. Eleven replicated measurements of 200.0 µmol·L-1 glucose solution gives a relative standard deviation (RSD) of 1.7%. The sensor exhibits good selectivity and stability and was successfully applied to the determination of glucose in real human serum samples. Schematic representation of one-step determination of serum glucose with GOx@Zn-ZIF-67 nanocomposite triggering cascade reactions between luminol and glucose.

Magnetic covalent organic framework immobilized gold nanoparticles with high-efficiency catalytic performance for chemiluminescent detection of pesticide triazophos.

Covalent organic frameworks (COFs) are considered to be a promising support material for catalyst due to their highly ordered porous structure. Here, a core-shell structured Fe3O4 magnetic covalent organic framework (Fe3O4@COF) was synthesized and employed to provide basic sites for immobilization of gold nanoparticles (AuNPs). The AuNPs was in-situ immobilized on the shell of Fe3O4@COF via a citrate reducing method. The Fe3O4@COF-AuNP had convenient magnetic separability and exhibited excellent mimicking peroxidase-like activity in catalyzing chemiluminescence (CL) reaction of luminol with hydrogen peroxide (H2O2). With acetylcholine chloride (ACh) as substrate of acetylcholinesterase (AChE), a CL method was exploited for sensitive detection of organophosphorus pesticide triazophos due to its irreversible inhibiting effect on the AChE activity and subsequently influences the production of H2O2 under the condition of choline oxidase (ChOx). This method gave a good linearity for triazophos in the range of 5.0-300.0 nmol L-1, and a limit of detection (LOD) of 1 nmol L-1 was acquired. The applicability of this method was verified by the determination of triazophos in different spiked vegetable samples.

AIEgens-based fluorescent covalent organic framework in construction of chemiluminescence resonance energy transfer system for serum uric acid detection.

A covalent organic framework (COF) with aggregation-induced emission (AIE) property was successfully synthesized through in situ marriage of a commonly used AIE molecule tetraphenylethylene (TPE) with Schiff base network (SNW-1) through a simple one-pot method. The TPE@SNW-1 was characterized with different techniques of Fourier transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy, scanning electron microscopy, and nitrogen adsorption/desorption experiments. The fluorescence of the TPE@SNW-1 strongly depends on the composition of tetrahydrofuran-water binary system. The AIE property of TPE@SNW-1 was directly supported with particle size distribution by dynamic light scattering technique. With the TPE@SNW-1 as an energy acceptor, a chemiluminescence resonance energy transfer (CRET) system was constructed with bis(2,4,6-trichlorophenyl) oxalate (TCPO)-hydrogen peroxide (H2O2) reaction as an energy donor. The chemiluminescence (CL) signal displays a good linear relationship with concentration of H2O2 in the 5.0-1000.0 µmol·L-1 range, and a detection limit of 2.34 µmol L-1. The system was further exploited to determine uric acid based on the fact that equal stoichiometric amount of H2O2 can be concurrently generated under the catalysis of uricase. The procedure exhibits a linear response to uric acid concentration in the range 10.0-150.0 µmol·L-1 and a detection limit of 4.94 µmol·L-1. The practicability of the method was demonstrated  in the determination of uric acid in human serum samples.

A novel peroxidase/oxidase mimetic Fe-porphyrin covalent organic framework enhanced the luminol chemiluminescence reaction and its application in glucose sensing.

A Fe-porphyrin covalent organic framework (Fe-PorCOF) was prepared through a postmodification strategy and characterized using different techniques. Fe-PorCOF exhibits an inherent peroxidase/oxidase mimetic catalytic activity and sharply accelerates chemiluminescence (CL) reactions between luminol and hydrogen peroxide (H2 O2 ) or dissolved oxygen (O2 ) under alkaline conditions. The catalytic role was attributed to a significant increase in production of reactive oxygen species. Using the imminent peroxidase mimetic catalytic activity of Fe-PorCOF, a new CL method was developed for determination of H2 O2 over a linear range from 0.01 to 10.0 µmol·L-1 and with a limit of detection of 5.3 nmol·L-1 . The combination of the peroxidase mimetic catalytic activity of Fe-PorCOF with the catalytic activity of glucose oxidase on glucose oxidation presents a sensitive CL method for glucose assay. The linear range and the detection limit for glucose were 0.05-8.0 µmol·L-1 and 4.0 nmol·L-1 , respectively. The practicability of this method was assessed by determination of glucose in human sera. As a peroxidase/oxidase mimetic, Fe-PorCOF is easy to prepare and exhibits good catalytic efficiency in the luminol reaction. We believe that this strategy will promote the development of a CL field with functional COFs as a catalyst.

In situ encapsulation of horseradish peroxidase in zeolitic imidazolate framework-8 enables catalyzing luminol reaction under near-neutral conditions for sensitive chemiluminescence determination of cholesterol.

HRP@ZIF-8 nanocomposite was prepared by in situ encapsulation of horseradish peroxidase (HRP) in the frame of zeolitic imidazolate framework-8 (ZIF-8) with a simple one-pot method. The HRP@ZIF-8 nanocomposite displays outstanding thermal stability and efficiently catalyzes the chemiluminescence (CL) reaction of luminol with hydrogen peroxide (H2O2) under near-neutral pH condition (pH 7-8). This CL system has a good response to H2O2 with a linear range of 0.1-100.0 µmol L-1. The limit of detection (LOD) is 0.06 µmol L-1 H2O2. By marriage with cholesterol oxidase, cholesterol is determined with a linear range from 0.1 to 100.0 µmol L-1 and a LOD of 0.04 µmol L-1. The relative standard deviations (RSD) are 1.7% and 2.5%, respectively, in 11 repeated measurements of 50.0 µmol L-1 solutions of H2O2 and cholesterol, indicating excellent precision of the method. The method shows good selectivity and has been applied to the determination of total cholesterol in real serum samples. No significant difference has been observed between the results obtained by this method and the cholesterol oxidase-peroxidase coupling method. Graphical abstract Schematic presentation of in situ one-pot synthesis of horseradish peroxidase@zeolitic imidazolate framework-8 (HRP@ZIF-8) nanocomposite and chemiluminescence determination of cholesterol with HRP@ZIF-8 catalyzing luminol-H2O2 system.

Luminescent metal organic frameworks-based chemiluminescence resonance energy transfer platform for turn-on detection of fluoride ion.

A luminescent metal organic frameworks (MOFs)-based chemiluminescence resonance energy transfer (CRET) platform was constructed for turn-on detection of fluoride ion. A hybrid MOFs was prepared by encapsulating strong fluorescence 2',7'-dichlorofluorescein (DCF) into the frames of NH2-MIL-101(Al) MOFs, which led to a significant suppression of fluorescence signal of DCF. In the presence of fluoride ion, it destroyed the structure of the hybrid MOFs and released DCF molecules from the frames due to the formation of more stable aluminum hexafluoride complex ions [AlF63-] between fluoride ion and aluminum ion. The released DCF molecules accepted the energy originating from the chemical reaction of bis(2,4,6-trichlorophenyl)oxalate (TCPO) with hydrogen peroxide (H2O2), producing a strong chemiluminescence (CL) emission. The CL signal was strong dependent on the concentration of fluoride ion presented and showed a linear response in the range of 0.5-80.0 µmol L-1 (9.5 µg L-1-1.52 mg L-1). The detection limit was 0.05 µmol L-1 (about 0.95 µg L-1) fluoride ion and the relative standard deviations was 2.3% for 40.0 µmol L-1 fluoride ion solution (n = 11). This MOFs-based CRET method was successfully applied to the determination of fluoride ion in drinking water samples, demonstrating its potential application in analysis of real samples.

A covalent triazine framework as an oxidase mimetic in the luminol chemiluminescence system: application to the determination of the antioxidant rutin.

It is found that a covalent triazine framework (CTF-1) (that was prepared from 1,4-dicyanobenzene) exhibits oxidase-like activity toward the oxidation of luminol with dissolved oxygen in alkaline condition to produce intense blue chemiluminescence (CL). The reaction follows Michaelis-Menten kinetics and shows strong specificity for luminol. Reactive oxygen species including 1O2, •OH and O2•- are testified to be involved in the reaction and responsible for the CL. The reaction was applied to the determination of the radical-scavenging activity of antioxidants, with rutin, kaempferol and ferulic acid serving as model scavengers. A sensitive CL method was developed for the determination of rutin based on its inhibitory effect on the reaction. The CL system gave a linear response to the concentration of rutin in the range of 0.03-0.25 µmol·L-1 with a limit of detection of 0.015 µmol·L-1. The practicability of the method was demonstrated by successful determination of rutin in tablets and in Flos Sophorae Immaturus. Graphical Abstract.

A colorimetric assay for acetylcholinesterase activity and inhibitor screening based on the thiocholine-induced inhibition of the oxidative power of MnO2 nanosheets on 3,3',5,5'-tetramethylbenzidine.

The authors describe a colorimetric method for the determination of the activity of acetylcholinesterase (AChE). Manganese dioxide (MnO2) nanosheets directly reacts with 3,3',5,5'-tetramethylbenzidine (TMB) in the absence of hydrogen peroxide (H2O2). This leads to the formation of a blue product (oxTMB) with an absorption peak at 652 nm. If AChE hydrolyzes its substrate acetylthiocholine chloride, thiocholine is formed which blocks the oxidative power of the MnO2 nanosheets. Hence, oxTMB will not be formed. The decreased absorbance is directly related to the AChE activity in the 0.01-1.0 mU·mL-1 range. The detection limit is 0.01 mU·mL-1 and the relative standard deviation is 1.2% (for n = 11 at 0.5 mU·mL-1). The method was also applied to screen for inhibitors of AChE. Graphical abstract Based on the oxidizing properties of manganese dioxide nanosheets (MnO2 nanosheets), we report a colorimetric method for determining acetylcholinesterase activity with the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB).

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 .).

The immunosuppressive characteristics of FB1 by inhibition of maturation and function of BMDCs.

Fumonisin B1 (FB1) is one kind of mycotoxins that has the neurotoxicity, carcinogenicity, hepatotoxicity and immunotoxicity produced by the fungus Fusarium verticillioides, which commonly infects corn and other crops and is harmful to animal and human health upon consumption of FB1-contaminated feed or food. However, the mechanism of immunotoxicity, especially the immunosuppression induced by FB1 is still unclear. The most pivotal cells in the induction of immune responses are dendritic cells (DCs). In this study, we used murine bone marrow-derived dendritic cells (BMDCs) as a model system to elucidate the effect of FB1 on the function of BMDCs through biological methods. We found that FB1 reversed the morphological changes and enhanced the endocytosis of FITC-dextran in LPS-treated BMDCs. At the same time, FB1 decreased the LPS-induced expressions of MHC II, C[1]D80 and CD86 molecules in BMDCs (p<0.05), as well as the T-cell stimulatory capacity of BMDCs (p<0.01). Moreover, the secretions of IL-6, IL-10 and IL-12, but not TNF-α induced by LPS exposure were suppressed by FB1 in a dose dependent (p<0.01). It was considered that the immunosuppressive effects of FB1 were mainly caused by changing the morphology and interfering with the process of antigen uptake, processing and presentation. The results highlighted that FB1 had the capacity to modulate the immune responses of BMDCs.