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Assessing the ergodicity of graphene liquid cell electron microscope measurements, we report that loop states of circular DNA interconvert reversibly and that loop numbers follow the Boltzmann distribution expected for this molecule in bulk solution, provided that the electron dose is low (80-keV electron energy and electron dose rate 1-20 e- Å-2 s-1). This imaging technique appears to act as a "slow motion" camera that reveals equilibrated distributions by imaging the time average of a few molecules without the need to image a spatial ensemble.
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Elétrons , Grafite , Microscopia Eletrônica , Movimento (Física) , Conformação de Ácido NucleicoRESUMO
BACKGROUND: Sarcopenia and obesity are two abnormal body composition phenotypes, and sarcopenic obesity (SO) is characterized by both low skeletal muscle mass (sarcopenia) and high adiposity (obesity). SO negatively influences the clinical status of patients with chronic obstructive pulmonary disease (COPD). However, the studies exploring the prevalence and clinical effects of SO in COPD patients are limited. Our study aimed to elucidate the prevalence and impact of SO on COPD patients. METHODS: In this cross-sectional study, the pulmonary function, St. George's Respiratory Questionnaire, exercise tolerance, body composition, and serum levels of resistin and TNF-α were assessed in 198 COPD patients. The clinical value of serum resistin and TNF-α for predicting SO in patients with COPD was evaluated. RESULTS: In the 198 patients with COPD, the prevalence rates of sarcopenia, obesity, and SO in COPD patients were 27.27%, 29.8%, and 9.6%, respectively. Patients with SO experienced more severe symptoms of dyspnea and worse health related quality of life. The expression of resistin increased in patients with SO compared to other patients. The AUC value of serum resistin level for predicting SO was 0.870 (95% CI: 0.799-0.940). BMI (OR: 1.474, 95% CI: 1.124-1.934) and resistin (OR: 1.001, 95% CI: 1.000-1.002) levels were independent risk factors of SO in patients with COPD in Multivariate analysis. CONCLUSION: The prevalence rates of SO in COPD patients was 9.6%. COPD accompanied by SO is significantly associated with worse pulmonary function and poor physical performance. Serum resistin may be a potential adjunct for predicting SO in COPD patients.
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Doença Pulmonar Obstrutiva Crônica , Sarcopenia , Humanos , Sarcopenia/complicações , Estudos Transversais , Resistina , Qualidade de Vida , Fator de Necrose Tumoral alfa , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Obesidade/complicações , Obesidade/epidemiologiaRESUMO
Portulaca oleracea L. (purslane) is a widely distributed plant with a long history of cultivation and consumption. Notably, polysaccharides obtained from purslane exhibit surprising and satisfactory biological activities, which explain the various benefits of purslane on human health, including anti-inflammatory, antidiabetic, antitumor, antifatigue, antiviral and immunomodulatory effects. This article systematically reviews the extraction and purification methods, chemical structure, chemical modification, biological activity and other aspects of polysaccharides from purslane collected in the Chinese Pharmacopoeia, Flora of China, Web of Science, PubMed, Baidu Scholar, Google Scholar and CNKI databases in the last 14 years, using the keywords "Portulaca oleracea L. polysaccharides" and "purslane polysaccharides". The application of purslane polysaccharides in different fields is also summarized, and its application prospects are also discussed. This paper provides an updated and deeper understanding of purslane polysaccharides, which will provide useful guidance for the further optimization of polysaccharide structures and the development of purslane polysaccharides as a novel functional material, as well as a theoretical basis for its further research and application in human health and manufacturing development.
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Portulaca , Humanos , Portulaca/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Hipoglicemiantes , ChinaRESUMO
Stretchable conductors capable of precise micropatterning are imperative for applications in various wearable technologies. Metallic nanoparticles with low aspect ratios and miniscule sizes are preferred over metallic nanowires or nanoflakes for such applications. However, nanoparticles tend to lose mutual contact during stretching. Therefore, they are rarely used alone in stretchable conductors. In this study, electronic inks comprising silver nanoparticles (AgNPs) for the high-resolution printing of stretchable conductors are reported. AgNPs are synthesized using aqueous polyurethane micelles, which are subsequently disentangled into polymeric chains in isopropanol to stabilize the inks. The ink rheology can be arbitrarily tuned to allow direct-write printing with a minimum feature width of 3 µm. Owing to the absence of extra surfactants, direct drying of such inks at room temperature provides the stretchable conductors with an initial conductivity of 8846 S cm-1 and conductivity of 1305 S cm-1 at 100% strain. This enhanced performance is attributed to the conductive percolations through assemblies of AgNPs adapting to the strain and is equivalent to those of stretchable conductors filled with Ag nanowires or flakes. These inks are promising for the scalable fabrication of highly integrated stretchable electronics.
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Recently, pressurized metered-dose inhalers (pMDIs) are getting more attention as an effective approach of pulmonary drug delivery, and nanoparticle-based formulations have become a new generation of pMDIs, especially for water insoluble drugs. Up until now, there is no clinical application of nanoparticle-based pMDIs. The main hurdle remains in the lack of knowledge of the in vivo fate of those systems. In this study, a fluorescent probe named P4 with aggregation-caused quenching (ACQ) effect was loaded in the nanoparticle-based pMDIs to track the in vivo fate. P4 probe expressed strong fluorescence when distributed in intact nanoparticles, but quenched in the in vivo aqueous environment due to molecular aggregation. Experimentally, P4 probe was encapsulated into solid lipid nanoparticles (SLN) as P4-SLN, and then, the formulation of pMDIs was optimized. The content (w/w) of the optimal formulation (P4-SLN-pMDIs) was as follows: 6.02% Pluronic® L64, 12.03% ethanol, 0.46% P4-SLN, and 81.49% 1,1,1,2-tetrafluoroethane (HFA-134a). P4-SLN-pMDI was transparent in appearance, possessed a particle size of 132.07 ± 3.56 nm, and the fine particle fraction (FPF) was 39.53 ± 1.94%, as well good stability was shown within 10 days. The results indicated P4-SLN-pMDI was successfully prepared. Moreover, the ACQ property of P4-SLN-pMDIs was verified, which ensured the fluorescence property as a credible tool for in vivo fate study. Taken together, this work established a platform that could provide a firm theoretical support for exploration of the in vivo fate of nanoparticle-based pMDIs in subsequent studies. Grapical abstract.
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Corantes Fluorescentes/química , Inaladores Dosimetrados , Administração por Inalação , Aerossóis/farmacologia , Hidrocarbonetos Fluorados/administração & dosagem , Pulmão/efeitos dos fármacos , Nanopartículas , Tamanho da Partícula , PressãoRESUMO
Gas-phase ion trap mass spectrometry experiments and density functional theory calculations have been used to examine the routes to the formation of the 1,8-naphthyridine (napy) ligated geminally dimetallated phenyl complexes [(napy)Cu2(Ph)]+, [(napy)Ag2(Ph)]+ and [(napy)CuAg(Ph)]+ via extrusion of CO2 or SO2 under collision-induced dissociation conditions from their corresponding precursor complexes [(napy)Cu2(O2CPh)]+, [(napy)Ag2(O2CPh)]+, [(napy)CuAg(O2CPh)]+ and [(napy)Cu2(O2SPh)]+, [(napy)Ag2(O2SPh)]+, [(napy)CuAg(O2SPh)]+. Desulfination was found to be more facile than decarboxylation. Density functional theory calculations reveal that extrusion proceeds via two transition states: TS1 enables isomerization of the O, O-bridged benzoate to its O-bound form; TS2 involves extrusion of CO2 or SO2 with the concomitant formation of the organometallic cation and has the highest barrier. Of all the organometallic cations, only [(napy)Cu2(Ph)]+ reacts with water via hydrolysis to give [(napy)Cu2(OH)]+, consistent with density functional theory calculations which show that hydrolysis proceeds via the initial formation of the adduct [(napy)Cu2(Ph)(H2O)]+ which then proceeds via TS3 in which the coordinated H2O is deprotonated by the coordinated phenyl anion to give the product complex [(napy)Cu2(OH)(C6H6)]+, which then loses benzene.
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We report new structural motifs for Cu nanoclusters that conceptually represent seed crystals for large face-centred cubic (FCC) crystal growth. Kinetically controlled syntheses, high resolution mass spectrometry experiments for determination of the dication formulae and crystallographic characterisation were carried out for [Cu18 H16 (DPPE)6 ][BF4 ][Cl] (DPPE=bis(diphenylphosphino)ethane) and [Cu16 H14 (DPPA)6 ][(BF4 )2 ] (DPPA=bis(diphenylphosphino)amine) polyhydrido nanoclusters, which feature the unprecedented bifrustum and frustum metal-core architecture in metal nanoclusters. The Cu18 nanocluster contains two Cu9 frustum cupolae and the Cu16 nanocluster has one Cu9 frustum cupola and a Cu7 distorted hexagonal-shape base. Gas-phase experiments revealed that both Cu18 H16 and Cu16 H14 cores can spontaneously release H2 upon removal of one bisphosphine capping ligand.
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A combination of gas-phase ion trap mass spectrometry experiments and density functional theory (DFT) calculations have been used to examine the role of substituents on the decarboxylation of 25 different coordinated aromatic carboxylates in binuclear complexes, [(napy)Cu2(O2CC6H4X)]+, where napy is the ligand 1,8-naphthyridine (molecular formula, C8H6N2) and X = H and the ortho ( o), meta ( m) and para ( p) isomers of F, Br, CN, NO2, CF3, OAc, Me and MeO. Two competing unimolecular reaction pathways were found: decarboxylation to give the organometallic cation [(napy)Cu2(C6H4X)]+ or loss of the neutral copper benzoate to yield [(napy)Cu]+. The substituents on the aryl group influence the branching ratios of these product channels, but decarboxylation is always the dominant pathway. Density functional theory calculations reveal that decarboxylation proceeds via two transition states. The first enables a change in the coordination mode of the coordinated benzoate in [(napy)Cu2(O2CC6H4X)]+ from the thermodynamically favoured O, O-bridged form to the O-bound form, which is the reactive conformation for the second transition state which involves extrusion of CO2 with concomitant formation of the CO2 coordinated organometallic cation, [(napy)Cu2(C6H4X)(CO2)]+, which then loses CO2 in the final step to yield [(napy)Cu2(C6H4X)]+. In all cases the barrier is highest for the second transition state. The o-substituted benzoates show a lower activation energy than the m-substituted ones, while the p-substituted ones have the highest energy, which is consistent with the experimentally determined normalised collision energy required to induce fragmentation of [(napy)Cu2(O2CC6H4X)]+.
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An electrospray ionization mass spectrometry (ESI-MS) survey of the types of cationic copper clusters formed from an acetonitrile solution containing a 1:1:20 mixture of tetrakis(acetonitrile)copper(I) tetrafluoroborate [Cu(MeCN)4(BF4)], bis(diphenylphosphino)amine (dppa = (Ph2P)2NH = L), and NaBH4 revealed a major peak, which based on both the accurate masses and isotope distribution was assigned as [Cu3(BH4)(H)(L)3]+. This prompted synthetic efforts resulting in isolation of the dppa ligated trinuclear copper hydride nanoclusters, [Cu3(µ2-Cl)(µ3-H)(L)3](BF4) and [Cu3(µ3-BH4)(µ3-H)(L)3](BF4), which were subsequently structurally characterized using high resolution ESI-MS, X-ray crystallography, NMR, and IR spectroscopy. The X-ray structures reveal a common structural feature of the cation, in which the three copper(I) ions adopt a planar trinuclear Cu3 geometry coordinated on the bottom face by a µ3-hydride and surrounded by three dppa ligands. ESI-MS of [Cu3(µ2-Cl)(µ3-H)(L)3](BF4) and [Cu3(µ3-BH4)(µ3-H)(L)3](BF4) produces [Cu3(µ2-Cl)(µ3-H)(L)3]+ and [Cu3(µ3-BH4)(µ3-H)(L)3]+. The unimolecular gas-phase ion chemistry of these cations was examined under multistage tandem mass spectrometry conditions using collision-induced dissociation (CID). CID of both cations proceeds via ligand loss to give [Cu3(µ3-H)(X)(L)2]+, which is in competition with BH3 loss in the case of X = BH4. DFT calculations on the fragmentation of [Cu3(µ3-BH4)(µ3-H)(LMe)3]+ suggest that BH3 loss produces the hitherto elusive [Cu3(µ3-H)(µ2-H)(LMe)3]+, which undergoes further fragmentation via H2 loss. CID of the deuterium labeled cluster [Cu3(µ3-D)(µ3-BD4)(L)3]+ reveals that the competing losses of ligand and BD3 yield [Cu3(µ3-BD4)(µ3-D)(L)2]+ and [Cu3(D)2(L)3]+ as primary products, which subsequently fragment via further losses of BD3 or a ligand to give [Cu3(D)2(L)2]+. The coordinated hydrides in the latter ion are activated toward elimination of D2 to give [Cu3(L)2]+. Loss of HD and 2HD are minor channels, consistent with higher DFT predicted endothermicities to form [Cu3(D)(L)(L-H)]+ and [Cu3(L-H)2]+.
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The high elasticity and excellent gas barrier properties of rubber composites make them irreplaceable in the field of sealing. Constructing a complicated barrier network to reduce free volume is crucial to improving gas barrier properties. In this research, liquid acrylonitrile-butadiene rubber/γ-Methacryloxypropyl trimethoxy silane (KH570) modified graphene oxide/butyl rubber composites (LNBR/KGO/IIR) were fabricated. A KGO lamellar network was constructed to resist gas diffusion in the IIR matrix. Meanwhile, LNBR macromolecules further occupied the free volume inside the IIR composites, thereby maximizing the retardation of the path of small molecule gas permeation. The modification of GO by KH570 was successfully demonstrated through FTIR and XRD. The grafting rate of KH570 was calculated to be approximately 71.4%. KGO was well dispersed in IIR due to emulsion compounding and the formation of lamellar networks. The 300% modulus, tensile strength and tear strength of KGO/IIR were improved by 43.5%, 39.1% and 14.8%, respectively, compared to those of the IIR composite. In addition, the introduction of LNBR resulted in a 44.2% improvement in the gas barrier performance of nitrogen permeability relative to the original IIR composite.
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Due to safety problems caused by the use of organic electrolytes in lithium-ion batteries and the high production cost brought by the limited lithium resources, water-based zinc-ion batteries have become a new research focus in the field of energy storage due to their low production cost, safety, efficiency, and environmental friendliness. This paper focused on vanadium dioxide and expanded graphite (EG) composite cathode materials. Given the cycling problem caused by the structural fragility of vanadium dioxide in zinc-ion batteries, the feasibility of preparing a new composite material is explored. The EG/VO2 composites were prepared by a simple hydrothermal method, and compared with the aqueous zinc-ion batteries assembled with a single type of VO2 under the same conditions, the electrode materials composited with high-purity sulfur-free expanded graphite showed more excellent capacity, cycling performance, and multiplicity performance, and the EG/VO2 composites possessed a high discharge ratio of 345 mAh g-1 at 0.1 A g-1, and the Coulombic efficiency was close to 100%. The EG/VO2 composite has a high specific discharge capacity of 345 mAh g-1 at 0.1 A g-1 with a Coulombic efficiency close to 100%, a capacity retention of 77% after 100 cycles, and 277.8 mAh g-1 with a capacity retention of 78% at a 20-fold increase in current density. The long cycle test data demonstrated that the composite with expanded graphite effectively improved the cycling performance of vanadium-based materials, and the composite maintained a stable Coulombic efficiency of 100% at a high current density of 2 A/g and still maintained a specific capacity of 108.9 mAh/g after 2000 cycles.
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Using nanobubbles as geometrical confinements, we create a thin water film (â¼10 nm) in a graphene liquid cell and investigate the evolution of its instability at the nanoscale under transmission electron microscopy. The breakdown of the water films, resulting in the subsequent formation and growth of nanodroplets, is visualized and generalized into different modes. We identified distinct droplet formation and growth modes by analyzing the dynamic processes involving 61 droplets and 110 liquid bridges within 31 Graphene Liquid Cells (GLCs). Droplet formation is influenced by their positions in GLCs, taking on a semicircular shape at the edge and a circular shape in the middle. Growth modes include liquid mass transfer driven by Plateau-Rayleigh instability and merging processes in and out-of-plane of the graphene interface. Droplet growth can lead to the formation of liquid bridges for which we obtain multiview projections. Data analysis reveals the general dynamics of liquid bridges, including drawing liquids from neighboring residual water films, merging with surrounding droplets, and merging with other liquid bridges. Our experimental observations provide insights into fluid transport at the nanoscale.
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Metal-nitrogen-carbon catalysts with hierarchically dispersed porosity are deemed as efficient geometry for oxygen reduction reaction (ORR). However, catalytic performance determined by individual and interacting sites originating from structural heterogeneity is particularly elusive and yet remains to be understood. Here, an efficient hierarchically porous Fe single atom catalyst (Fe SAs-HP) is prepared with Fe atoms densely resided at micropores and mesopores. Fe SAs-HP exhibits robust ORR performance with half-wave potential of 0.94 V and turnover frequency of 5.99 e-1s-1site-1 at 0.80 V. Theoretical simulations unravel a structural heterogeneity induced optimization, where mesoporous Fe-N4 acts as real active centers as a result of long-range electron regulation by adjacent microporous sites, facilitating O2 activation and desorption of key intermediate *OH. Multilevel operando characterization results identify active Fe sites undergo a dynamic evolution from basic Fe-N4 to active Fe-N3 under working conditions. Our findings reveal the structural origin of enhanced intrinsic activity for hierarchically porous Fe-N4 sites.
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Silicosis is the most common type of pneumoconiosis, having a high incidence in workers chronically exposed to crystalline silica (CS). No specific medication exists for this condition. GHK, a tripeptide naturally occurring in human blood and urine, has antioxidant effects. We aimed to investigate the therapeutic effect of GHK-Cu on silicosis and its potential underlying molecular mechanism. An experimental silicosis mouse model was established to observe the effects of GHK-Cu on lung inflammation and fibrosis. Moreover, the effects of GHK-Cu on the alveolar macrophages (AM) were examined using the RAW264.7 cell line. Its molecular target, peroxiredoxin 6 (PRDX6), has been identified, and GHK-Cu can bind to PRDX6, thus attenuating lung inflammation and fibrosis in silicosis mice without significant systemic toxicity. These effects were partly related to the inhibition of the CS-induced oxidative stress in AM induced by GHK-Cu. Thus, our results suggest that GHK-Cu acts as a potential drug by attenuating alveolar macrophage oxidative stress. This, in turn, attenuates the progression of pulmonary inflammation and fibrosis, which provides a reference for the treatment of silicosis.
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Cobre , Modelos Animais de Doenças , Macrófagos Alveolares , Oligopeptídeos , Estresse Oxidativo , Peroxirredoxina VI , Silicose , Animais , Silicose/tratamento farmacológico , Silicose/metabolismo , Silicose/patologia , Camundongos , Cobre/química , Oligopeptídeos/farmacologia , Peroxirredoxina VI/metabolismo , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Células RAW 264.7 , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Pneumonia/tratamento farmacológico , Pneumonia/metabolismo , Pneumonia/patologia , Humanos , Masculino , Antioxidantes/farmacologiaRESUMO
BACKGROUND: Sarcopenia, characterized by progressive muscle dysfunction, is a common complication of chronic obstructive pulmonary disease (COPD). Our previous study revealed serum Lipoprotein-associated phospholipaseA2 (Lp-PLA2) level significantly increased in COPD and associated with exercise tolerance. This study further investigated the functions and target potential of Lp-PLA2 for sarcopenia in COPD. METHODS: The circulating Lp-PLA2 level/enzyme activity in COPD patients and age-matched healthy volunteers were measured. Clinical parameters on skeletal muscle were measured and their correlations with Lp-PLA2 were analyzed. We explored the involvement of Lp-PLA2 in vivo and treatment effectiveness of darapladib (a specific Lp-PLA2 inhibitor) in CS-induced muscle dysfunction models. RESULTS: Circulating Lp-PLA2 level/enzyme activity was elevated in COPD patients compared with healthy controls, negatively associated with skeletal muscle mass and function. In CS-induced muscle dysfunction murine models, up-regulated serum Lp-PLA2 level/enzyme activity was verified again. In CS-exposed mouse models, darapladib treatment reversed muscle mass loss and muscle dysfunction, meanwhile rescued upregulation of MuRF1 and atrogin-1, and activation of inflammatory factors, oxidant enzymes and NF-κB signaling. CONCLUSIONS: Lp-PLA2 could be a potential indicator for sarcopenia in COPD. Darapladib, a Lp-PLA2 inhibitor, can alleviate CS-induced skeletal muscle dysfunction and represents a potential therapeutic for sarcopenia in COPD.
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1-Alquil-2-acetilglicerofosfocolina Esterase , Doença Pulmonar Obstrutiva Crônica , Sarcopenia , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/complicações , Humanos , Sarcopenia/tratamento farmacológico , Sarcopenia/etiologia , 1-Alquil-2-acetilglicerofosfocolina Esterase/metabolismo , 1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Masculino , Animais , Camundongos , Feminino , Idoso , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Benzaldeídos/farmacologia , Benzaldeídos/uso terapêutico , Oximas/uso terapêutico , Oximas/farmacologia , Biomarcadores/sangue , Modelos Animais de Doenças , Compostos de Bifenilo , Dietilaminas , Pirimidinonas , SulfetosRESUMO
The development of facile, efficient synthesis method to construct low-cost and high-performance single-atom catalysts (SACs) for oxygen reduction reaction (ORR) is extremely important, yet still challenging. Herein, an atomically dispersed N, S co-doped carbon with abundant vacancy defects (NSC-vd) anchored Fe single atoms (SAs) is reported and a vacancy defects inductive effect is proposed for promoting electrocatalytic ORR. The optimized catalyst featured of stable FeâN3 S1 active sites exhibits excellent ORR activity with high turnover frequency and mass activity. In situ Raman, attenuated total reflectance surface enhanced infrared absorption spectroscopy reveal the FeâN3 S1 active sites exhibit different kinetic mechanisms in acidic and alkaline solutions. Operando X-ray absorption spectra reveal the ORR activity of Fe SAs/NSC-vd catalyst in different electrolyte is closely related to the coordination structure. Theoretical calculation reveals the upshifted d band center of FeâN3 S1 active sites facilitates the adsorption of O2 and accelerates the kinetics process of *OH reduction. The abundant vacancy defects around the FeâN3 S1 active sites balance the OOH* formation and *OH reduction, thus synergetically promoting the electrocatalytic ORR process.
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Ever-growing demands for rechargeable zinc-air batteries (ZABs) call for efficient bifunctional electrocatalysts. Among various electrocatalysts, single atom catalysts (SACs) have received increasing attention due to the merits of high atom utilization, structural tunability, and remarkable activity. Rational design of bifunctional SACs relies heavily on an in-depth understanding of reaction mechanisms, especially dynamic evolution under electrochemical conditions. This requires a systematic study in dynamic mechanisms to replace current trial and error modes. Herein, fundamental understanding of dynamic oxygen reduction reaction and oxygen evolution reaction mechanisms for SACs is first presented combining in situ and/or operando characterizations and theoretical calculations. By highlighting structure-performance relationships, rational regulation strategies are particularly proposed to facilitate the design of efficient bifunctional SACs. Furthermore, future perspectives and challenges are discussed. This review provides a thorough understanding of dynamic mechanisms and regulation strategies for bifunctional SACs, which are expected to pave the avenue for exploring optimum single atom bifunctional oxygen catalysts and effective ZABs.
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BACKGROUND: Skeletal muscle dysfunction is an important co-morbidity in patients with chronic obstructive pulmonary disease (COPD) and is significantly associated with increased mortality. Oxidative stress has been demonstrated an important trigger for COPD-related skeletal muscle dysfunction. Glycine-histidine-lysine (GHK) is an active tripeptide, which is a normal component of human plasma, saliva, and urine; promotes tissue regeneration; and acts as an anti-inflammatory and antioxidant properties. The purpose of this study was to determine whether GHK is involved in COPD-related skeletal muscle dysfunction. METHODS: The plasma GHK level in patients with COPD (n = 9) and age-paired healthy subjects (n = 11) were detected using reversed-phase high-performance liquid chromatography. The complex GHK with Cu (GHK-Cu) was used in in vitro (C2C12 myotubes) and in vivo experiments (cigarette smoking [CS]-exposure mouse model) to explore the involvement of GHK in CS-induced skeletal muscle dysfunction. RESULTS: Compared with healthy control, plasma GHK levels were decreased in patients with COPD (70.27 ± 38.87 ng/mL vs. 133.0 ± 54.54 ng/mL, P = 0.009). And plasma GHK levels in patients with COPD were associated with pectoralis muscle area (R = 0.684, P = 0.042), inflammatory factor TNF-α (R = -0.696, P = 0.037), and antioxidative stress factor SOD2 (R = 0.721, P = 0.029). GHK-Cu was found to rescue CSE-induced skeletal muscle dysfunction in C2C12 myotubes, as evidenced by increased expression of myosin heavy chain, reduced expression of MuRF1 and atrogin-1, elevated mitochondrial content, and enhanced resistance to oxidative stress. In CS-induced muscle dysfunction C57BL/6 mice, GHK-Cu treatment (0.2 and 2 mg/kg) reduces CS-induced muscle mass loss (skeletal muscle weight (1.19 ± 0.09% vs. 1.29 ± 0.06%, 1.40 ± 0.05%; P < 0.05) and muscle cross-sectional area elevated (1055 ± 552.4 µm2 vs. 1797 ± 620.9 µm2 , 2252 ± 534.0 µm2 ; P < 0.001), and also rescues CS-induced muscle weakness, indicated by improved grip strength (175.5 ± 36.15 g vs. 257.6 ± 37.98 g, 339.1 ± 72.22 g; P < 0.01). Mechanistically, GHK-Cu directly binds and activates SIRT1(the binding energy was -6.1 kcal/mol). Through activating SIRT1 deacetylation, GHK-Cu inhibits FoxO3a transcriptional activity to reduce protein degradation, deacetylates Nrf2 and contribute to its action of reducing oxidative stress by generation of anti-oxidant enzymes, increases PGC-1α expression to promote mitochondrial function. Finally, GHK-Cu could protect mice against CS-induced skeletal muscle dysfunction via SIRT1. CONCLUSIONS: Plasma glycyl-l-histidyl-l-lysine level in patients with chronic obstructive pulmonary disease was significantly decreased and was significantly associated with skeletal muscle mass. Exogenous administration of glycyl-l-histidyl-l-lysine-Cu2+ could protect against cigarette smoking-induced skeletal muscle dysfunction via sirtuin 1.
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Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Humanos , Camundongos , Animais , Lisina/metabolismo , Sirtuína 1/metabolismo , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismoRESUMO
Background: Sarcopenia often occurs as a comorbidity in many diseases which ultimately affects patient prognosis. However, it has received little attention in patients with idiopathic pulmonary fibrosis (IPF). This systematic review and meta-analysis aimed at determining the prevalence and risk factors of sarcopenia in patients with IPF. Methods: Embase, MEDLINE, Web of Science, and Cochrane databases were searched using relevant MeSH terms until December 31, 2022. The Newcastle-Ottawa Scale (NOS) was used for quality assessment and data analysis were performed using Stata MP 17.0 (Texas, USA). A random effects model was adopted to account for differences between articles, and the I2 statistic was used to describe statistical heterogeneities. Overall pooled estimates obtained from a random effects model were estimated using the metan command. Forest plots were generated to graphically represent the data of the meta-analysis. Meta-regression analysis was used for count or continuous variables. Egger test was used to evaluate publication bias and, if publication bias was observed, the trim and fill method was used. Main results: The search results showed 154 studies, and five studies (three cross-section and two cohort studies) with 477 participants were finally included. No significant heterogeneity was observed among studies included in the meta-analysis (I2 = 16.00%) and our study's publication bias is low (Egger test, p = 0.266). The prevalence of sarcopenia in patients with IPF was 26% (95% CI, 0.22-0.31). The risk factors for sarcopenia in patients with IPF were age (p = 0.0131), BMI (p = 0.001), FVC% (p < 0.001), FEV1% (p = 0.006), DLco% (p ≤ 0.001), and GAP score (p = 0.003). Conclusions: The pooled prevalence of sarcopenia in patients with IPF was 26%. The risk factors for sarcopenia in IPF patients were age, BMI, FVC%, FEV1%, DLco%, and GAP score. It is important to identify these risk factors as early as possible to improve the life quality of patients with IPF.
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It remains challenging to understand the structural evolution of conjugated polymers from single chains to solvated aggregates and film microstructures, although it underpins the performance of optoelectrical devices fabricated via the mainstream solution processing method. With several ensemble visual measurements, here we unravel the morphological evolution process of a model system of isoindigo-based conjugated molecules, including the hidden molecular assembly pathways, the mesoscale network formation, and their unorthodox chain dependence. Short chains show rigid chain conformations forming discrete aggregates in solution, which further grow to form a highly ordered film that exhibits poor electrical performance. In contrast, long chains exhibit flexible chain conformations, creating interlinked aggregates networks in solution, which are directly imprinted into films, forming interconnective solid-state microstructure with excellent electrical performance. Visualizing multi-level assembly structures of conjugated molecules provides a deep understanding of the inheritance of assemblies from solution to solid-state, accelerating the optimization of device fabrication.