In the study, papain was chosen from five proteases to hydrolyze proteins of monkfish swim bladders for effectively utilizing monkfish (
) processing byproducts, and the hydrolysis conditions of ...papain were optimized as hydrolysis temperature of 65 °C, pH 7.5, enzyme dose 2.5% and time 5 h using single-factor and orthogonal experiments. Eighteen peptides were purified from the swim bladder hydrolysate of monkfish by ultrafiltration and gel permeation chromatography methods and identified as YDYD, QDYD, AGPAS, GPGPHGPSGP, GPK, HRE, GRW, ARW, GPTE, DDGGK, IGPAS, AKPAT, YPAGP, DPT, FPGPT, GPGPT, GPT and DPAGP, respectively. Among eighteen peptides, GRW and ARW showed significant DPPH· scavenging activities with EC
values of 1.053 ± 0.003 and 0.773 ± 0.003 mg/mL, respectively; YDYD, QDYD, GRW, ARW and YPAGP revealed significantly HO· scavenging activities with EC
values of 0.150 ± 0.060, 0.177 ± 0.035, 0.201 ± 0.013, 0.183 ± 0.0016 and 0.190 ± 0.010 mg/mL, respectively; YDYD, QDYD, ARW, DDGGK and YPAGP have significantly O2-· scavenging capability with EC
values of 0.126 ± 0.0005, 0.112 ± 0.0028, 0.127 ± 0.0002, 0.128 ± 0.0018 and 0.107 ± 0.0002 mg/mL, respectively; and YDYD, QDYD and YPAGP showed strong ABTS
· scavenging ability with EC
values of 3.197 ± 0.036, 2.337 ± 0.016 and 3.839 ± 0.102 mg/mL, respectively. YDYD, ARW and DDGGK displayed the remarkable ability of lipid peroxidation inhibition and Ferric-reducing antioxidant properties. Moreover, YDYD and ARW can protect Plasmid DNA and HepG2 cells against H
O
-induced oxidative stress. Furthermore, eighteen isolated peptides had high stability under temperatures ranging from 25-100 °C; YDYD, QDYD, GRW and ARW were more sensitive to alkali treatment, but DDGGK and YPAGP were more sensitive to acid treatment; and YDYD showed strong stability treated with simulated GI digestion. Therefore, the prepared antioxidant peptides, especially YDYD, QDYD, GRW, ARW, DDGGK and YPAGP from monkfish swim bladders could serve as functional components applied in health-promoting products because of their high-antioxidant functions.
Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, smooth muscle cell proliferation, cell apoptosis, necrosis, fibrosis, and local inflammation. Immune and ...inflammatory responses have significant effects on every phase of atherosclerosis, and increasing evidence shows that immunity plays a more important role in atherosclerosis by tightly regulating its progression. Therefore, understanding the relationship between immune responses and the atherosclerotic microenvironment is extremely important. This article reviews existing knowledge regarding the pathogenesis of immune responses in the atherosclerotic microenvironment, and the immune mechanisms involved in atherosclerosis formation and activation.
Nanoscale metal–organic frameworks (NMOFs) have proven to be a class of promising drug carriers as a result of their high porosity, crystalline nature with definite structure information, and ...potential for further functionality. However, MOF‐based drug carriers with active tumor‐targeting function have not been extensively researched until now. Here we show a strategy for constructing active tumor‐targeted NMOF drug carriers by anchoring functional folic acid (FA) molecules onto the metal clusters of NMOFs. Two zirconium‐based MOFs, MOF‐808 and NH2‐UiO‐66, were chosen as models to reduce to the nanoscale for application as drug carriers, and then the terminal carboxylates of FA molecules were coordinated to Zr6 clusters on the surfaces of the nanoparticles by substitution of the original formate or terminal ‐OH ligands. The successful modification with FA was confirmed by solid‐state 13C MAS NMR and UV/Vis spectroscopy and other characterization methods. Drug loading and controlled release behavior at different pH were determined by utilizing the anticancer drug 5‐fluorouracil (5‐FU) as the model drug. Confocal laser scanning microscopy measurements further demonstrated that 5‐FU‐loaded FA‐NMOFs have excellent targeting ability through the efficient cellular uptake of FA‐NMOFs. This work opens up a new avenue to the construction of active tumor‐targeted NMOF‐based drug carriers with potential for cancer therapies.
Targeted drug delivery: Nanoscale metal–organic frameworks modified with folic acid (FA‐NMOFs) have been prepared as potential drug carriers for targeted delivery to tumor cells (see figure). The anticancer drug 5‐fluorouracil (5‐FU) was encapsulated in the pores of the FA‐NMOFs. The 5‐FU‐loaded FA‐NMOFs showed excellent biocompatibility and were found to effectively kill tumor cells through the targeting effect of the FA‐NMOFs.
In this study, we investigate the ameliorating functions of QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) from monkfish swim bladders on an FFA-induced NAFLD model of HepG2 ...cells. The lipid-lowering mechanisms revealed that these five oligopeptides can up-regulate the expression of phospho-AMP-activated protein kinase (
-AMPK) proteins to inhibit the expression of the sterol regulatory element binding protein-1c (SREBP-1c) proteins on increasing lipid synthesis and up-regulating the expression of the PPAP-α and CPT-1 proteins on promoting the β-oxidation of fatty acids. Moreover, QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) can significantly inhibit reactive oxygen species' (ROS) production, promote the activities of intracellular antioxidases (superoxide dismutase, SOD; glutathione peroxidase, GSH-PX; and catalase, CAT) and bring down the content of malondialdehyde (MDA) derived from lipid peroxidation. Further investigations revealed that the regulation of these five oligopeptides on oxidative stress was achieved through activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to raise the expression levels of the heme oxygenase 1 (HO-1) protein and downstream antioxidant proteases. Therefore, QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) could serve as candidate ingredients to develop functional products for treating NAFLD.
Covalent organic frameworks (COFs) are an emerging type of crystalline and porous photocatalysts for hydrogen evolution, however, the overall water splitting activity of COFs is rarely known. In this ...work, we firstly realized overall water splitting activity of β-ketoamine COFs by systematically engineering N-sites, architecture, and morphology. By in situ incorporating sub-nanometer platinum (Pt) nanoparticles co-catalyst into the pores of COFs nanosheets, both Pt@TpBpy-NS and Pt@TpBpy-2-NS show visible-light-driven overall water splitting activity, with the optimal H
and O
evolution activities of 9.9 and 4.8 μmol in 5 h for Pt@TpBpy-NS, respectively, and a maximum solar-to-hydrogen efficiency of 0.23%. The crucial factors affecting the activity including N-sites position, nano morphology, and co-catalyst distribution were systematically explored. Further mechanism investigation reveals the tiny diversity of N sites in COFs that induces great differences in electron transfer as well as reaction potential barriers.
Covalent‐organic frameworks (COFs) have been recognized as a new type of promising photocatalysts for hydrogen evolution. To investigate how different functional groups attached in the backbone of ...COFs affect the overall photocatalytic H2 evolution, for the first time, we selected and synthesized a series of ketoenamine‐based COFs with the same host framework as model system. It includes TpPa−COF−X (X=−H, −(CH3)2, and −NO2) with three different groups attached in the backbone of TpPa−COF. We systematically investigated the differences in morphology, light‐absorption intensity and band gap of these 2D COFs. The results of photocatalytic H2 evolution measurements indicate that the TpPa−COF−(CH3)2 shows the best activity, while the activity of TpPa−COF−NO2 is relatively low compared to that of other two COFs in the system. Moreover, the separation ability of photogenerated charge was also followed the order of TpPa−COF−(CH3)2>TpPa−COF>TpPa−COF−NO2. The best photocatalytic H2 production performance of TpPa−COF−(CH3)2 in these systems should be mainly attributed to the better electron‐donating ability of −CH3 groups compared to −H or −NO2 group, which result in more efficient charge transferring in the inner of the material. This work demonstrates that reasonably adding electron‐donating group in TpPa−COFs can lead to a better photocatalytic H2 evolution activity, and which is meaningful for further design of efficient COF‐based photocatalysts for H2 evolution.
Photocatalysis: A series ketoenamine‐based COFs of TpPa−COF−X (X=−H, −(CH3)2, and −NO2) exhibit significant difference on the visible light absorbance and efficiency of photocatalytic H2 evolution, which can be attributed to strengthen charge carrier mobilities both in‐plane and in the stacking direction because of the electron‐donating groups.
Perovskite Light‐emitting diodes (PeLEDs) have emerged as a promising technique for future high‐definition displays due to their outstanding electroluminescent characters. However, the development of ...blue PeLEDs toward practical applications is seriously hindered by their inferior performance, which mainly arises from the detrimental halide ionic behavior and thus severe nonradiative recombination in mixed‐halide blue perovskite materials. Herein, efficient sky‐blue PeLEDs featuring spectrally stable emission at 483 nm are realized by employing bifunctional passivators of Lewis‐base benzoic acid anions and alkali metal cations to simultaneously passivate the under‐coordinated lead atoms and suppress halide ion migration. A decent external quantum efficiency (EQE) of 16.58% and a maximum EQE of 18.65% are achieved, which is further boosted to 28.82% through the optical outcoupling enhancement. This work demonstrates unique insight into the generality and individuality of this category of benzoates and puts forward a feasible guidance in choosing appropriate additives for efficient perovskite materials.
Defect passivation and the suppression of halide ion migration are simultaneously achieved in mixed‐halide perovskite materials via the incorporation of bifunctional additives containing Lewis‐base group and alkali metal ions. Efficient sky‐blue perovskite light‐emitting diodes achieve an external quantum efficiency of 16.58%, which is further boosted to 28.82% by the optical outcoupling enhancement.
Perovskite light‐emitting didoes (PeLEDs) have shown considerable potential in solution‐processable display applications. However, the performance of blue PeLEDs in terms of efficiency and stability ...hinders their practicality on account of severe trap‐mediated nonradiative recombination losses and halide phase segregation. To ameliorate these issues, mixed‐halide sky‐blue perovskite materials are strategically modulated through crystal defect passivation with a trifurcate isocyanate oligomer, which leads to the synergistical suppression of charge trap density and halide ion migration. The proposed approach enables the performance improvement for sky‐blue PeLEDs, exhibiting a peak external quantum efficiency of 14.82% and spectrally stable emission at 487 nm. In addition, prolonged operational lifetime and enhanced capability of moisture resistance are achieved simultaneously, approaching a half‐lifetime of ≈2900 s at an initial brightness of 178 cd m–2.
A trifurcate isocyanate oligomer is proposed for modulating mixed‐halide sky‐blue perovskite materials by passivating crystal defects, suppressing halide ion migration, and resisting moisture simultaneously. Sky‐blue perovskite light‐emitting diodes achieve a high external quantum efficiency of 14.82% and distinctly improved operational stability with a half‐lifetime of ≈3000 s.
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•Deep learning-based algorithm for estimating the local quality of 3D cryo-EM density maps using Q-score as reference.•Estimating accurate map-model fit score with only cryo-EM map as ...the input.•Low root mean squared error on the test set with reported resolutions.•Fast and parameter-free software for users to use.
Cryogenic electron microscopy maps are valuable for determining macromolecule structures. A proper quality assessment method is essential for cryo-EM map selection or revision. This article presents DeepQs, a novel approach to estimate local quality for 3D cryo-EM density maps, using a deep-learning algorithm based on map-model fit score. DeepQs is a parameter-free method for users and incorporates structural information between map and its related atomic model into well-trained models by deep learning. More specifically, the DeepQs approach leverages the interplay between map and atomic model through predefined map-model fit score, Q-score. DeepQs can get close results to the ground truth map-model fit scores with only cryo-EM map as input. In experiments, DeepQs demonstrates the lowest root mean square error with standard method Fourier shell correlation metric and high correlation with map-model fit score, Q-score, when compared with other local quality estimation methods in high-resolution dataset (<=5 Å). DeepQs can also be applied to evaluate the quality of the post-processed maps. In both cases, DeepQs runs faster by using GPU acceleration. Our program is available at http://www.csbio.sjtu.edu.cn/bioinf/DeepQs for academic use.
NALA (ClinicalTrials.gov identifier: NCT01808573) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine ...(N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens.
Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m
twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m
twice a day 14 d/21 d). Coprimary end points were centrally confirmed progression-free survival (PFS) and overall survival (OS). NALA was considered positive if either primary end point was met (α split between end points). Secondary end points were time to CNS disease intervention, investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate, safety, and health-related quality of life (HRQoL).
A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314). Centrally reviewed PFS was improved with N+C (hazard ratio HR, 0.76; 95% CI, 0.63 to 0.93; stratified log-rank
0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07;
2098). Fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8%
29.2%;
043). ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4;
1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 to 0.74;
.0004). The most common all-grade adverse events were diarrhea (N+C 83%
L+C 66%) and nausea (53%
42%). Discontinuation rates and HRQoL were similar between groups.
N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed.
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