The extrapolation strategy raised by Nesterov, which can accelerate the convergence rate of gradient descent methods by orders of magnitude when dealing with smooth convex objective, has led to tremendous success in t...
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Limited therapeutic options are available to effectively preventing atherosclerosis. Inflammatory endothelial cells, foamy macrophages, and high protease levels contribute to atherosclerotic plaque formation. Studies ...
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Limited therapeutic options are available to effectively preventing atherosclerosis. Inflammatory endothelial cells, foamy macrophages, and high protease levels contribute to atherosclerotic plaque formation. Studies have shown that catechins effectively scavenge reactive oxygen species (ROS), inhibit monocyte adhesion and reduce cholesterol levels, while nitric oxide (NO) enhances endothelial function. However, due to the poor stability and bioavailability of catechins and the toxicity from the burst release of current synthetic small molecules NO donor, effective delivery of these bioactive compounds to treat atherosclerosis is still a challenge. Herein, a catechin/protein-based NO donor co-delivery nanosystem was designed for combinatorial anti-atherosclerotic therapy. We engineered a (−)-epigallocatechin-3-gallate (EGCG)/NO-releasing protein co-assembled nanocomplex based on specific catechin-protein interactions. Furthermore, the nanocomplex was surface modified with fucoidan (Fu), a sulfated polysaccharide with anti-inflammatory activity. This nanocomplex exhibits sensitivity to ROS, ph, and enzymes. The Fu-functionalized nanoparticles specifically accumulates in atherosclerotic plaques mediated by P-selectin on inflamed endothelial cells and scavenger receptor A (SR-A) on foamy macrophages. Under environmental stimuli that simulate the condition of plaque, the nanoparticles are readily activated to release EGCG and NO in response to excess ROS and high protease levels, exerting the multi-synergistic anti-atherosclerosic effects on reducing monocyte adhesion, promoting NO production to proliferate endothelial cells, lowering ROS levels, anddecreasing the foam cell formation in vitro, and reducing lipid accumulation, plaque size, and inflammatory cytokines release in high-fat diet-induced atherosclerosis model in ApoE−/− mice. The integration of plaques targeting ability and multiple therapeutic functions can provide an advanced therapeutic strategy for athero
The circular economy concept has recently gained prominence in political debate and corporate discourse around the world as a pathway towards sustainability. The academic debate is characterised by several and sometim...
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Background: Hemodialysis holds the highest incidence and prevalence rate in Taiwan globally. However, the implementation of advance care planning (ACP), advance directives (Ad), and patient self-determination acts (PS...
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Background: Hemodialysis holds the highest incidence and prevalence rate in Taiwan globally. However, the implementation of advance care planning (ACP), advance directives (Ad), and patient self-determination acts (PSdA) remains limited. Our objective was to examine the current status of ACP, Ad and PSdA and potential opportunities for enhancement. Methods: We developed a novel questionnaire to assess individuals’ knowledge, attitudes, and intentions regarding ACP, Ad, and PSdA. We also collected baseline characteristics and additional inquiries for correlation analysis to identify potential factors. Student’s t-test and Analysis of Variance were employed to assess significance. Results: Initially, a cohort of 241 patients was initially considered for inclusion in this study. Subsequently, 135 patients agreed to participate in the questionnaire study, resulting in 129 valid questionnaires. Among these respondents, 76 were male (59.9%), and 53 were female (41.1%). Only 13.2% had signed Ad. A significant portion (85.3%) indicated that they had not discussed their dialysis prognosis with healthcare providers. Additionally, a mere 14% engaged in conversations about life-threatening decisions. Ninety percent believed that healthcare providers had not furnished information about ACP, and only 30% haddiscussed such choices with their families. The findings revealed that the average standardized score for ACP and Ad goals was 84.97, while the attitude towards PSdA received a standardized score of 69.94. The intention score stood at 69.52 in standardized terms. Potential candidates for ACP initiation included individuals aged 50 to 64, possessing at least a college education, being unmarried, and having no history of diabetes. Conclusion: Patients undergoing hemodialysis exhibited a significant knowledge gap concerning ACP, Ad, and the PSdA. Notably, a substantial number of dialytic patients had not received adequate information on these subjects. Nevertheless, they display
To bridge western and traditional Chinese medicine, research in Chinese medicinal herbs has become an increasing trend for discovering new effective antiviral drugs. In addition, this pioneer study disclosed that syne...
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This paper presents an adaptive prediction-based control scheme for developing an ecological cruise control (ECC) system when simultaneous running on the roads with the continuous curves and up-down slopes, which aims...
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BACKGROUNd ANd PURPOSE:Acute respiratory distress syndrome (ARdS) is a catastrophic pulmonary inflammatory dysfunction with a high mortality rate. An overwhelming immune response by neutrophils is a key feature in inf...
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BACKGROUNd ANd PURPOSE:Acute respiratory distress syndrome (ARdS) is a catastrophic pulmonary inflammatory dysfunction with a high mortality rate. An overwhelming immune response by neutrophils is a key feature in infective or sterile ARdS. The formyl peptide receptor 1 (FPR1) is a crucial damage-sensing receptor for inflammatory reactions in the initiation and progression of neutrophil-mediated ARdS. However, effective targets for controlling dysregulated neutrophilic inflammatory injuries in ARdS are limited.
EXPERIMENTAL APPROACH:Human neutrophils were used to explore the anti-inflammatory effects of cyclic lipopeptide anteiso-C13-surfactin (IA-1) from marine Bacillus amyloliquefaciens. The lipopolysaccharide-induced model of ARdS in mice was used to determine the therapeutic potential of IA-1 in ARdS. Lung tissues were harvested for histology analyses.
KEY RESULTS:The lipopeptide IA-1 inhibited immune responses of neutrophils, including respiratory burst, degranulation, and expression of adhesion molecules. IA-1 inhibited the binding of N-formyl peptides to FPR1 in human neutrophils and in hFPR1-transfected HEK293 cells. We identified IA-1 as a competitive FPR1 antagonist, thus diminishing the downstream signalling pathways involving calcium, mitogen-activated protein kinases and Akt. Furthermore, IA-1 ameliorated the inflammatory damage to lung tissue, by decreasing neutrophil infiltration, reducing elastase release and oxidative stress in endotoxemic mice.
CONCLUSION ANd IMPLICATIONS:The lipopeptide IA-1 could serve as a therapeutic option for ARdS by inhibiting FPR1-mediated neutrophilic injury.
Background and Aims: We investigated the use of GnRHa pretreatment with different protocols anddurations of treatment on pregnancy outcomes in women undergoing FET with artificial cycles (AC-FET). Method: A systemati...
Background and Aims: We investigated the use of GnRHa pretreatment with different protocols anddurations of treatment on pregnancy outcomes in women undergoing FET with artificial cycles (AC-FET). Method: A systematic search of PubMed, EMBASE, Google Scholar, and Cochrane library was performed to include only eligible peer-reviewed studies in English published before September 01, 2022. This review was registered on PROSPERO (CRd42022299259) Results: A total of 41 studies (43021 individuals) were included with low to moderate risk of bias. Overall, GnRHa pretreatment improved clinical pregnancy rate (CPR) (OR=1.27, 95%CI:1.12-1.44), implantation rate (IR) (OR=1.24, 95%CI:1.07-1.45), live birth rate (LBR) (OR=1.31, 95%CI:1.07-1.60) and endometrial thickness (Md=0.16, 95%CI:0.03-0.30). Subgroup analyses of randomized and non-randomized studies both demonstrated the benefits of GnRHa pretreatment in CPR, IR, and LBR. Protocols using depot GnRHa (OR=1.19, 95%CI:1.04-1.36) showed a better LBR than daily GnRHa (OR=1.04, 95%CI:0.93-1.16). Women administered GnRHa for more than one cycle had better CPR (OR=2.01, 95%CI:1.29-3.13) and IR (OR=2.14, 95%CI:0.98-4.67) than those treated with GnRHa within one cycle before FET ([OR=1.18, 95%CI:1.04-1.33] and [OR=1.16, 95%CI:1.01-1.32], respectively). In women with PCOS, pituitary suppression with GnRHa significantly improved CPR (OR=1.24, 95%CI:0.98-4.67), LBR (OR=1.22, 95%CI:1.05-1.42) and reduced the miscarriage rate (OR=0.75, 95%CI:0.59-0.95). In contrast, women with regular menstruation had a higher endometrial thickness (Md=0.16, 95%CI: 0.04-0.28) but no significant improvements in pregnancy outcomes. GnRHa pretreatment considerably improved IR (OR=2.21, 95%CI:1.60-3.07) in women with adenomyosis and CPR (OR=1.74, 95%CI:1.12-2.71), and LBR (OR=1.67, 95%CI:1.06-2.63) in women with endometriosis. Conclusion: GnRHa pretreatment, especially with longer suppression duration and the use of depot GnRHa, demonstrates a beneficial rol
BACKGROUNd:The main commercially available methods for detecting small molecules of mycotoxins in traditional Chinese medicine (TCM) and functional foods are enzyme-linked immunosorbent assay and mass spectrometry. Re...
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BACKGROUNd:The main commercially available methods for detecting small molecules of mycotoxins in traditional Chinese medicine (TCM) and functional foods are enzyme-linked immunosorbent assay and mass spectrometry. Regarding the development of diagnostic antibody reagents, effective methods for the rapid preparation of specific monoclonal antibodies are inadequate.
METHOdS:In this study, a novel synthetic phage-displayed nanobody Golden Glove (SynaGG) library with a glove-like cavity configuration was established using phage display technology in synthetic biology. We applied this unique SynaGG library on the small molecule aflatoxin B1 (AFB1), which has strong hepatotoxicity, to isolate specific nanobodies with high affinity for AFB1.
RESULT:These nanobodies exhibit no cross-reactivity with the hapten methotrexate, which is recognized by the original antibody template. By binding to AFB1, two nanobodies can neutralize AFB1-induced hepatocyte growth inhibition. Using molecular docking, we found that the unique non-hypervariable complementarity-determining region 4 (CdR4) loop region of the nanobody was involved in the interaction with AFB1. Specifically, the CdR4's positively charged amino acid arginine directed the binding interaction between the nanobody and AFB1. We then rationally optimized the interaction between AFB1 and the nanobody by mutating serine at position 2 into valine. The binding affinity of the nanobody to AFB1 was effectively improved, and this result supported the use of molecular structure simulation for antibody optimization.
CONCLUSION:In summary, this study revealed that the novel SynaGG library, which was constructed through computer-aideddesign, can be used to isolate nanobodies that specifically bind to small molecules. The results of this study could facilitate the development of nanobody materials to detect small molecules for the rapid screening of TCM materials and foods in the future.
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