RESUMO
BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare interstitial lung disease characterised by the accumulation of lipoprotein material in the alveoli. Although dyslipidaemia is a prominet feature, the causal effect of lipid traits on PAP remains unclear. This study aimed to explore the role of lipid traits in PAP and evaluate the potential of lipid-lowering drug targets in PAP. METHODS: Clinical outcomes, lipid profiles and lung function tests were analysed in a clinical cohort of diagnosed PAP patients and propensity score-matched healthy controls. Genome-wide association study data on PAP, lipid metabolism, blood cells and variants of genes encoding potential lipid-lowering drug targets were obtained for Mendelian randomisation (MR) and mediation analyses. FINDINGS: Observational results showed that higher levels of total cholesterol (TC), triglycerides and low-density lipoprotein (LDL) were associated with increased risks of PAP. Higher levels of TC and LDL were also associated with worse PAP severity. In MR analysis, elevated LDL was associated with an increased risk of PAP (OR: 4.32, 95% CI: 1.63 to 11.61, p=0.018). Elevated monocytes were associated with a lower risk of PAP (OR 0.34, 95% CI: 0.18 to 0.66, p=0.002) and mediated the risk impact of LDL on PAP. Genetic mimicry of PCSK9 inhibition was associated with a reduced risk of PAP (OR 0.03, p=0.007). INTERPRETATION: Our results support the crucial role of lipid and metabolism-related traits in PAP risk, emphasising the monocyte-mediated, causal effect of elevated LDL in PAP genetics. PCSK9 mediates the development of PAP by raising LDL. These finding provide evidence for lipid-related mechanisms and promising lipid-lowering drug target for PAP.
Assuntos
Pró-Proteína Convertase 9 , Proteinose Alveolar Pulmonar , Humanos , HDL-Colesterol/genética , LDL-Colesterol/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Metabolismo dos Lipídeos/genética , Pró-Proteína Convertase 9/genética , Proteinose Alveolar Pulmonar/genética , Análise da Randomização MendelianaRESUMO
A coordination macrocycle composed of eight identical [PMo8O27]- ({PMo8}) clusters connected by both organic tetraphosphonates and inorganic phosphates, (C3N2H5)29(NH4)6H12[(PMo8O27)8(C10P4O12N2H20)4(PO4)4Cs(Mo4O10(H2O)4)] (C3N2H5+ = imidazolium), is presented here. The primary building block, {PMo8}, is a tetravacant Keggin-type phosphomolybdate that has never been observed before. The compound shows a high proton conductivity of 9.70 × 10-3 S cm-1 at 373 K and 98% relative humidity. Control experiments on an imidazolium-free sample demonstrate the critical role of the imidazolium counterions as mobile proton carriers. The contribution of imidazolium necessitates a high activation energy (Ea = 0.502 eV) for proton conduction via the vehicle mechanism.
RESUMO
In the present study, ultrasound-assisted extraction (UAE) of crude polysaccharides (PSP) from pumpkin seeds was optimized by response surface method (RSM). The polysaccharide yield (2.29 ± 0.14%), which agreed closely with the theoretical predicted value 2.40%, was obtained under the optimal extraction conditions: extraction time 24 min, extraction temperature 50 °C, ultrasonic power 347 W, and liquid to solid ratio 23 mL/g. After further purification by two-step column chromatography, a novel polysaccharide (PSP-1) was isolated from pumpkin seeds. PSP-1 was composed of mannose, glucose, and galactose in a molar ratio of 1.00:4.26:5.78 with molecular weight of 3728 g/mol. 1D and 2D NMR spectroscopy analysis revealed that the backbone of PSP-1 was mainly formed by ßâ6)-ß-d-Galp-(1â, â6)-α-d-Glcp-(1â, and â3,6)-ß-d-Manp-(1â with branching at O-3 and O-6 of â3,6)-ß-d-Manp-(1â. Branch linkages were composed of α-d-Glcp-(1â and â4)-α-d-Galp-(1â.
Assuntos
Fracionamento Químico/métodos , Cucurbita/química , Polissacarídeos/análise , Sementes/química , Ondas Ultrassônicas , Antioxidantes/análise , Carboidratos da Dieta/análise , Hexoses/química , Modelos Moleculares , Estrutura Molecular , Peso MolecularRESUMO
The coupling of functionalized inorganic polyoxometalates with polymer electrolytes leads to considerably enhanced mechanical properties and faster ion transport (1.1 × 10-4 S cm-1) at room temperature. The assembled Li/Li symmetric cell displays excellent stability in a 3000 h cycling test and a Li/LiFePO4 cell exhibits superior cycling performance over 250 cycles.
RESUMO
Ultrasonic-assisted enzymatic extraction (UAEE) technology was employed to extract the polysaccharides from dandelion leaves (DLP). The extraction conditions were optimized by response surface method (RSM) and Box-Behnken design (BBD). The polysaccharide yield (14.05⯱â¯0.95%), which well matched with the predicted value of 14.27%, was obtained under the optimum parameters: ultrasound power 500â¯W, ultrasound time 42â¯min, cellulase amount 4.90%, and particle size 80â¯mesh. After purification by AB-8 Macroporous Resin and Sephadex G-100 column, a novel polysaccharide (DLP-I) was isolated and its molecular weight was estimated to be 87,000â¯g/mol by high performance liquid chromatography (HPLC). Gas chromatography (GC) analysis showed that DLP-I was composed of rhamnose, arabinose, mannose, galactose and glucose in the molar ratio of 1.14:1.00:1.05:4.76:1.52. 1D and 2D NMR spectra confirmed that the backbone of DLP-I was mainly consisted of â4)-α-D-Galp-(1â, â4)-ß-D-Manp-(1â, â4)-α-D-Glcp-(1â, â2,4)-α-L-Rhap-(1â, and α-L-Araf-(1â with branching at O-2 and O-4 of â2,4)-α-L-Rhap-(1â. In addition, the digestion results showed DLP-I could keep its stability during the simulated digestive juices.
Assuntos
Folhas de Planta/química , Polissacarídeos/isolamento & purificação , Taraxacum/química , Ultrassom/métodos , Análise de Variância , Espectroscopia de Ressonância Magnética , Tamanho da Partícula , Polissacarídeos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Fatores de TempoRESUMO
Ag-ZnO co-sputtered films at various atomic ratios of Ag (Ag/(Ag + Zn) at.%) were prepared by a radio frequency magnetron cosputtering system, using the co-sputtered targets of Ag and ZnO. The activation of the Ag acceptors (AgZn) and the formation of the Ag aggregations (Ag°) in the ZnO matrix were investigated from XRD, Raman scattering, and XPS measurements. The Ag-ZnO co-sputtered film behaving like a p-type conduction was achievable after annealing at 350 °C under air ambient for 1 h.