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Covalent organic frameworks (COFs), known for their chemical stability and porous crystalline structure, hold promises as advanced separation membranes. However, fabricating high-quality COF membranes, particularly on industrial-preferred hollow fiber substrates, remains challenging. This study introduces a novel vapor/vapor-solid (V/V-S) method for growing ultrathin crystalline TpPa-1 COF membranes on the inner lumen surface of alumina hollow fibers (TpPa-1/Alumina). Through vapor-phase monomer introduction onto polydopamine-modified alumina at 170 °C and 1â atm, efficient polymerization and crystallization occur at the confined V-S interface. This enables one-step growth within 8â h, producing 100â nm thick COF membranes with strong substrate adhesion. TpPa-1/Alumina exhibits exceptional stability and performance over 80â h in continuous cross-flow organic solvent nanofiltration (OSN), with methanol permeance of about 200â L m-2 h-1 bar-1 and dye rejection with molecular weight cutoff (MWCO) of approximately 700â Da. Moreover, the versatile V/V-S method synthesizes two additional COF membranes (TpPa2Cl/Alumina and TpHz/Alumina) with different pore sizes and chemical environments. Adjusting the COF membrane thickness between 100-500â nm is achievable easily by varying the growth cycle numbers. Notably, TpPa2Cl/Alumina demonstrates excellent OSN performance in separating the model active pharmaceutical ingredient glycyrrhizic acid (GA) from dimethyl sulfoxide (DMSO), highlighting the method's potential for large-scale industrial applications.
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OBJECTIVE: The aim of this study was to establish reference values for rate of torque development (RTD) and muscle torque steadiness (MTS) of knee extensors across the lifespan, and evaluate if these measures are independently associated with Osteoarthritis Research Society International (OARSI)-recommended performance-based measures (6-minute walk test, 30-second chair stand test, stair climb test) and other clinical variables. METHODS: In this cross-sectional observational study, knee extensor strength of 764 participants (12-89 years) from the 1000 Norms Project was assessed via fixed dynamometry. Age- and sex-stratified normative RTD (Nms-1 kg-1) and MTS (Nm kg-1) values were presented as means and 95% confidence intervals. Correlations and multiple regression analyses were calculated to identify factors (age, sex, height, weight, OARSI-recommended performance-based measures, Knee Injury and Osteoarthritis Outcome Score, vertical jump, long jump, grip strength, basic gait-related knee biomechanics) independently associated with RTD or MTS. RESULTS: Age- and sex-stratified normative RTD and MTS reference values were generated. Male subjects exhibited higher RTD but poorer MTS (less steady) than female subjects across all age groups. Better performance in OARSI-recommended performance-based measures, vertical jump, long jump, and grip strength were associated with greater RTD but poorer MTS. Thirty-second chair stand test, stair climb test, vertical jump, long jump, and grip strength were independent determinants of RTD and MTS. CONCLUSIONS: The RTD and MTS demonstrated associations with clinical variables relevant to knee osteoarthritis. The normative reference values generated may help identify the presence and extent of impairments in RTD and MTS associated with knee osteoarthritis and assist in developing responsive outcome measures for therapeutic trials.
Assuntos
Força Muscular , Músculo Esquelético , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Valores de Referência , TorqueRESUMO
Bile acids (BA) are synthesized in the human liver and undergo metabolism by host gut bacteria. In diseased states, gut microbial dysbiosis may lead to high primary unconjugated BA concentrations and significant perturbations to secondary BA. Hence, it is important to understand the microbial-mediated formation kinetics of secondary bile acids using physiologically relevant ex vivo human faecal microbiota models. Here, we optimized an ex vivo human faecal microbiota model to recapitulate the metabolic kinetics of primary unconjugated BA and applied it to investigate the formation kinetics of novel secondary BA metabolites and their sequential pathways. We demonstrated (1) first-order depletion of primary BA, cholic acid (CA) and chenodeoxycholic acid (CDCA), under non-saturable conditions and (2) saturable Michaelis-Menten kinetics for secondary BA metabolite formation with increasing substrate concentration. Notably, relatively lower Michaelis constants (Km) were associated with the formation of deoxycholic acid (DCA, 14.3 µM) and lithocholic acid (LCA, 140 µM) versus 3-oxo CA (>1000 µM), 7-keto DCA (443 µM) and 7-keto LCA (>1000 µM), thereby recapitulating clinically observed saturation of 7α-dehydroxylation relative to oxidation of primary BA. Congruently, metagenomics revealed higher relative abundance of functional genes related to the oxidation pathway as compared to the 7α-dehydroxylation pathway. In addition, we demonstrated gut microbial-mediated hyocholic acid (HCA) and hyodeoxycholic acid (HDCA) formation from CDCA. In conclusion, we optimized a physiologically relevant ex vivo human faecal microbiota model to investigate gut microbial-mediated metabolism of primary BA and present a novel gut microbial-catalysed two-step pathway from CDCA to HCA and, subsequently, HDCA.