Notes

Piecewise-linear embeddings of tangles as well as links with rotoinversion proportion.
190 (95% CI 0.133, 0.247), 0.184 (95% CI 0.117, 0.252), and 0.194 (95% CI 0.086, 0.301). Mediation analysis showed that visceral fat accumulation contributed to 51.37%, 53.85%, and 26.51% of obesity-induced hepatic steatosis in the total, female, and male subjects, respectively.

Visceral fat accumulation partially mediates obesity-induced hepatic steatosis in overweight and obese individuals, especially in women. More focus on visceral fat reduction is needed in obese individuals.
Visceral fat accumulation partially mediates obesity-induced hepatic steatosis in overweight and obese individuals, especially in women. More focus on visceral fat reduction is needed in obese individuals.Objective This study was conducted to investigate the association between genetic variants in histone modification regions and clinical outcomes of PEM chemotherapy in patients with lung adenocarcinoma. Methods Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The associations of 279 SNPs with chemotherapy response and overall survival (OS) were analyzed in 314 lung adenocarcinoma patients who underwent PEM chemotherapy. Results Among the SNPs investigated, 18 were significantly associated with response to chemotherapy, while 28 with OS. Of these SNPs, rs549794A>G in an enhancer which is expected to regulate the expression of ribosomal protein S3 (RPS3) gene was significantly associated with both worse response to chemotherapy and worse OS (adjusted odds ration [aOR] = 0.59, 95% CI = 0.36-0.97, P = 0.04; adjusted hazard ratio [aHR] = 1.44, 95% CI = 1.09-1.91, P = 0.01, respectively). Previous studies suggested that RPS3, a multi-functional protein with various extraribosomal activities, may play a role in chemotherapy resistance. Therefore, it is postulated that rs549794-induced change in the expression level of RPS3 may affect the response to PEM chemotherapy and consequently the survival outcomes in lung adenocarcinoma patients. Conclusion This study suggests that genetic variants in the histone modification regions may be useful for the prediction of clinical outcomes of PEM chemotherapy in advanced lung adenocarcinoma.Based on the multitarget strategy, a series of novel clioquinol-1-benzyl-1,2,3,6-tetrahydropyridine hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation in vitro revealed that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE). The optimal compound, 19n, exhibited excellent AChE inhibitory potency (IC50 = 0.11 μM), appropriate metal chelating functions, modulation of AChE- and metal-induced Aβ aggregation, neuroprotection against okadaic acid-induced mitochondrial dysfunction and ROS damage, and interesting properties that reduced p-Tau levels in addition to no toxicity on SH-SY5Y cells observed at a concentration up to 50 μM. selleck inhibitor Most importantly, compound 19n was more well tolerated (>1200 mg/kg) than donepezil (LD50 = 28.124 mg/kg) in vivo. Moreover, compound 19n demonstrated marked improvements in cognitive and spatial memory in two AD mice models (scopolamine-induced and Aβ1-42-induced) and suppressed inflammation induced by Aβ1-42 in the cortex. The multifunctional profiles of compound 19n demonstrate that it deserves further investigation as a promising lead in the development of innovatively multifunctional drugs for Alzheimer's disease.A total of twenty-five novel carboxylic acid, methylester, methylamide or cyano nonsteroidal anti-inflammatory drug (NSAID) derivatives incorporating Se in the chemical form of selenoester were reported. Twenty Se-NSAID analogs exhibited an increase in cytotoxic potency compared with parent NSAID scaffolds (aspirin, salicylic acid, naproxen, indomethacin and ketoprofen). Top five analogs were selected to further study their cytotoxicity in a larger panel of cancer cells and were also submitted to the DTP program of the NCI's panel of 60 cancer cell lines. Compounds 4a and 4d stood out with IC50 values below 10 μM in several cancer cells along with a selectivity index higher than 5 in breast cancer cells. Remarkably, analog 4d was found to inhibit cell growth notably in two breast cancer cell lines by inducing apoptosis, and to be metabolized to release the parent NSAID along with the Se fragment. Taken together, our results show that Se-NSAID analog 4d could be a potential chemotherapeutic drug for breast cancer.Phosphatidylinositol 3-kinase gamma (PI3Kγ) plays a critical role in immune signaling, thus identifying PI3Kγ as a potential therapeutic target. However, developing selective PI3Kγ inhibitors is hampered by the highly conserved structure of the ATP-binding pocket. Focused effort would be needed to improve upon the γ-subtype selectivity of the inhibitors; therefore, in the present study, a naïve Bayesian classification (NBC) model with PI3Kγ structural features that integrates molecular docking and pharmacophore based on multiple PI3Kγ conformations was developed for virtual screening against PI3Kγ to find novel selective PI3Kγ inhibitors. First, the active PI3Kγ inhibitors/decoy dataset was used to prove whether molecular docking or pharmacophore, integrating multiple PI3Kγ conformations always has higher prediction accuracy than that of any single conformation. Second, both internal cross-validation and external prediction revealed that the NBC model combining molecular docking and pharmacophore could significantly improve the enrichment of active PI3Kγ inhibitors. Then, an analog dataset based on JN-PK1 (a reference compound) was constructed and submitted to virtual screening using the optimal NBC model. Finally, a novel inhibitor with higher PI3Kγ inhibitory activity than JN-PK1 was identified through a series of biological assays, showing both good accuracy and significant reliability of the NBC model with the PI3Kγ structural features. We hope that the developed virtual screening strategy will provide valuable guidance for the discovery of novel selective PI3Kγ inhibitors.In recent times, carbon dots (CDs) are emerging for numerous interdisciplinary applications by modulating their inherent chemical functionality during or post-synthesis modification. The current study reports the hydrothermal synthesis of polyvinylpyrrolidone K-30 (PVP) passivated clove bud-derived carbon dots (PPCCDs) for multifaceted applications. The adopted technique is facile and environmentally friendly for the production of CDs with in situ PVP passivation. Physicochemical characterization of CDs is performed using various spectroscopic and microscopic techniques. The study reveals the formation of nitrogen-doped spherical PPCCDs with an average hydrodynamic size of ∼ 4.9 nm. It is also evident that there is modulation in optical properties and quantum efficiency as a result of PVP passivation. The study further demonstrates their suitability in biological environments as observed by pH stability, photostability, and cytocompatibility results. PPCCDs have shown significant antioxidant activity against DPPH (EC50 57 µg/mL), suppression of superoxide anion radical (EC50 53 µg/mL), and an efficient catalytic activity towards degradation of Rhodamine-B (Rh-B) dye. UV-Visible spectroscopy unveil the reaction mechanism during antioxidant and catalytic activities of CDs that are validated by Electron paramagnetic resonance (EPR) spectroscopy with an indication of effective electron or proton donating abilities. Its bioimaging potential is evidenced through cellular fluorescence imaging with 3T3 and L929 cell lines.Diabetic retinopathy (DR) is a severe ocular complication that causes retinal damage, being one of the leading causes of blindness globally, thus the development of new strategies to prevent and treat DR as well as other degenerative diseases is highly desired. This work is focused on the design and fabrication of an ingenious model of polymeric microcapsules (MC) for controlled drug delivery in human retina cells able to carry therapeutic resveratrol (RSV) molecules in tandem with active anisotropic gold bipyramidal nanoparticles (AuBPs) as efficient photothermal agents. Specifically, MC were developed via a Layer-by-Layer deposition technique, by successively adding oppositely charged polyelectrolytes on a RSV-conjugated calcium carbonate (CaCO3) core. For the monitorization and localization of the as-formed spherical fluorescent MC inside human retina pigmented epithelial (RPE) D407 cells, fluorescein isothiocyanate, a Food and Drug Administration approved fluorophore, was attached between the polyelectrolytes layers. High-performance liquid chromatography analysis revealed a loading efficiency of over 90% of RSV on the CaCO3 core and demonstrates its release upon NIR irradiation as a consequence of the thermoplasmonic effect of MC. The cytotoxicity of the RSV-carrying MC inside human retina cells was assessed by WST-1 assay. Finally, cellular internalization and localization of the MC inside living RPE cells were monitored via Conventional Fluorescence and Re-Scanning Confocal Fluorescence Microscopy. This research seeks to take use of the novel MC and implement them as potential intraocular RSV delivery vehicles for the therapy of DR.Adipose-derived mesenchymal stem cells (ADSCs) have beneficial effects in cell transplantation therapy; these cells are collected from adipose tissue using low-invasive methods. However, to prepare ADSCs for cell therapy, a cell separation method that neither involves modification of the cell surface nor causes loss of cell activity is needed. Here, we aimed to develop ADSC separation columns using thermoresponsive cationic block copolymer brush-grafted beads as packing materials. The block copolymer brush was formed by a bottom cationic segment, poly(N,N-dimethylaminopropylacrylamide) (PDMAPAAm), and an upper thermoresponsive segment, poly(N-isopropylacrylamide) (PNIPAAm), and was grafted in two atom transfer radical polymerization reactions. The copolymer brush-grafted silica beads were packed into a column. An ADSC suspension was introduced into the columns at 37 °C and adsorbed on the copolymer brush-modified beads through electrostatic and hydrophobic interactions with the PDMAPAAm and PNIPAAm segments, respectively. The adsorbed ADSCs eluted from the column by lowering the temperature to 4 °C. In contrast, most Jurkat and vascular endothelial cells eluted at 37 °C, because of the relatively weaker electrostatic interactions with the block copolymer brush compared to ADSCs. Using the prepared column, a mixture of ADSCs and Jurkat cells was separated by changing the column temperature. The recovered ADSCs exhibited cell activity. The developed cell separation column may be useful for isolating ADSCs without cell surface modification, while maintaining cell activity.Automatic polyp segmentation can help physicians to effectively locate polyps (a.k.a. region of interests) in clinical practice, in the way of screening colonoscopy images assisted by neural networks (NN). However, two significant bottlenecks hinder its effectiveness, disappointing physicians' expectations. (1) Changeable polyps in different scaling, orientation, and illumination, bring difficulty in accurate segmentation. (2) Current works building on a dominant decoder-encoder network tend to overlook appearance details (e.g., textures) for a tiny polyp, degrading the accuracy to differentiate polyps. For alleviating the bottlenecks, we investigate a hybrid semantic network (HSNet) that adopts both advantages of Transformer and convolutional neural networks (CNN), aiming at improving polyp segmentation. Our HSNet contains a cross-semantic attention module (CSA), a hybrid semantic complementary module (HSC), and a multi-scale prediction module (MSP). Unlike previous works on segmenting polyps, we newly insert the CSA module, which can fill the gap between low-level and high-level features via an interactive mechanism that exchanges two types of semantics from different NN attentions.
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