RESULTS: Heat and UHP treatments induced the unfolding of DLp to varied degrees, as revealed by fluorescence spectroscopy, ultraviolet-visible absorption, circular dichroism spectra and surface hydrophobicity measurements. Two types of heating-denatured states with varied unfolding degrees were obtained, while UHP at both levels of 100/500 MPa caused partial unfolding of DLp and the presence of a molten-globule state, which significantly enhanced the binding affinity between DLp and (E,E)-2,4-heptadienal. In particular, significantly modified secondary structures of DLp were observed in heating-denatured samples. Excessive denaturing and unfolding degrees resulted in no significant changes in the absorption behavior of the volatile ligand, as characterized by observations of fluorescence quenching and analysis of headspace concentrations.
CONCLUSION: Defining process-induced conformational transition behavior of matrix proteins could be a promising strategy to regulate food flavor attributes and, particularly, to produce DLp coextracted with limited off-flavor components by modifying their interaction during extraction processes. © 2023 Society of Chemical Industry.
METHODS: G. lucidum samples from various sources and in varying stages were identified by using δ 13C, δD, δ 18O, δ 15N, C, and N contents combined with chemometric tools. Chemometric approaches, including PCA, OPLS-DA, PLS, and FLDA models, were applied to the obtained data. The established models were used to trace the origin of G. lucidum from various sources or track various stages of G. lucidum.
RESULTS: In the stage model, the δ 13C, δD, δ 18O, δ 15N, C, and N contents were considered meaningful variables to identify various stages of G. lucidum (bud development, growth, and maturing) using PCA and OPLS-DA and the findings were validated by the PLS model rather than by only four variables (δ 13C, δD, δ 18O, and δ 15N). In the origin model, only four variables, namely δ 13C, δD, δ 18O, and δ 15N, were used. PCA divided G. lucidum samples into four clusters: A (Zhejiang), B (Anhui), C (Jilin), and D (Fujian). The OPLS-DA model could be used to classify the origin of G. lucidum. The model was validated by other test samples (Pseudostellaria heterophylla), and the external test (G. lucidum) by PLS and FLDA models demonstrated external verification accuracy of up to 100%.
CONCLUSION: C, H, O, and N stable isotopes and C and N contents combined with chemometric techniques demonstrated considerable potential in the geographic authentication of G. lucidum, providing a promising method to identify stages of G. lucidum.
METHODS: Expression of SPRY genes in human and mice PDAC was analyzed using The Cancer Genome Atlas and Gene Expression Omnibus datasets, and by immunohistochemistry analysis. Gain-of-function, loss-of-function of Spry1 and orthotopic xenograft model were adopted to investigate the function of Spry1 in mice PDAC. Bioinformatics analysis, transwell and flowcytometry analysis were used to identify the effects of SPRY1 on immune cells. Co-immunoprecipitation and K-ras4B G12V overexpression were used to identify molecular mechanism.
RESULTS: SPRY1 expression was remarkably increased in PDAC tissues and positively associated with poor prognosis of PDAC patients. SPRY1 knockdown suppressed tumor growth in mice. SPRY1 was found to promote CXCL12 expression and facilitate neutrophil and macrophage infiltration via CXCL12-CXCR4 axis. Pharmacological inhibition of CXCL12-CXCR4 largely abrogated the oncogenic functions of SPRY1 by suppressing neutrophil and macrophage infiltration. Mechanistically, SPRY1 interacted with ubiquitin carboxy-terminal hydrolase L1 to induce activation of nuclear factor κB signaling and ultimately increase CXCL12 expression. Moreover, SPRY1 transcription was dependent on KRAS mutation and was mediated by MAPK-ERK signaling.
CONCLUSION: High expression of SPRY1 can function as an oncogene in PDAC by promoting cancer-associated inflammation. Targeting SPRY1 might be an important approach for designing new strategy of tumor therapy.
METHODS: Analyses were conducted post hoc of this 24-month, phase III, double-blind study, in which RRMS patients were randomized (1:1:1) to once daily oral fingolimod 0.5 mg, 1.25 mg or placebo. The key outcomes were the association between baseline RNFLT and baseline clinical characteristics and clinical/imaging outcomes up to 24 months. Change of RNFLT with fingolimod versus placebo within 24 months and time to retinal nerve fiber layer (RNFL) thinning were evaluated.
RESULTS: Altogether 885 patients were included. At baseline, lower RNFLT was correlated with higher Expanded Disability Status Scale score (r = -1.085, p = 0.018), lower brain volume (r = 0.025, p = 0.006) and deep gray matter volume (r = 0.731, p
OBJECTIVE: This meta-analysis aimed to identify risk factors for inadequate bowel preparation in older patients.
METHODS: PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases were searched from their inception to February 2023. Cohort and cross-sectional studies exploring the risk factors for inadequate bowel preparation were included in this systematic review. Odds ratio (OR) values from individual studies were pooled using fixed-effects and random-effects models. In addition, a sensitivity analysis and assessment of publication bias were performed.
RESULTS: This meta-analysis included six studies (n = 1553) on previous abdominal surgery, six studies (n = 1494) on constipation, seven studies (n = 1505) on diabetes, eight studies (n = 2093) on non-compliance with the diet regimen, seven studies (n = 1350) on incomplete intake of laxative, and nine studies (n = 2163) on inadequate exercise during preparation. The pooled analysis showed that history of abdominal surgery (OR = 2.72; 95 % confidence interval, CI: 2.07 to 3.56), constipation (OR = 3.56, 95 % CI: 2.41 to 5.25), diabetes (OR = 2.54, 95 % CI: 1.81 to 3.57), non-compliance with the diet regimen (OR = 2.51, 95 % CI: 1.96 to 3.21), incomplete intake of laxative (OR = 2.43, 95 % CI: 1.60 to 3.67), and inadequate exercise during preparation (OR = 3.13, 95 % CI: 2.39 to 4.11) were independent risk factors for inadequate bowel preparation in older patients undergoing colonoscopy.
CONCLUSIONS: Three comorbid factors and three behavioral factors were significantly associated with inadequate bowel preparation in older adults. This meta-analysis provides valuable information for developing predictive models of poor bowel preparation.
METHODS: Phase III, randomized, double-blind, placebo-controlled study (EP0083; NCT03083665) evaluating BRV 50 mg/day and 200 mg/day in patients (≥16-80 years) with FOS with/without secondary generalization (focal to bilateral tonic-clonic seizures) despite current treatment with 1 or 2 concomitant antiseizure medications. Following an 8-week baseline, patients were randomized 1:1:1 to placebo, BRV 50 mg/day, or BRV 200 mg/day, and entered a 12-week treatment period. Efficacy outcomes: percent reduction over placebo in 28-day FOS frequency (primary); 50% responder rate in FOS frequency; median percent reduction in FOS frequency from baseline; seizure freedom during treatment period (secondary). Primary safety endpoints: incidences of treatment-emergent adverse events (TEAEs); TEAEs leading to discontinuation; serious TEAEs.
RESULTS: In this study, 448/449 randomized patients (mean age, 34.5 years; 53.8% female) received ≥1 dose of study medication (placebo/BRV 50 mg/BRV 200 mg/day: n = 149/151/148). Percent reduction over placebo in 28-day adjusted FOS frequency was 24.5% (p = 0.0005) and 33.4% (p