Hydrophilic interaction liquid chromatography (HILIC) is a useful tool in glycoproteomic analysis. Glutathione (GSH) is a well-known zwitterionic tripeptide with great hydrophilicity and ...biocompatibility and is ubiquitous in biological activities. In this study, a hydrophilic metal-organic framework (denoted as mMOF@Au@GSH) was synthesized by grafting glutathione on Au-immobilized magnetic MOFs via the affinity between the thiol group in glutathione and Au. Endowed with the high hydrophilicity of glutathione, the large surface area of the MOF and strong magnetic responsiveness of magnetic nanoparticles, the as-prepared mMOF@Au@GSH exhibited high selectivity (1 : 100) and great sensitivity (0.5 fmol μL-1) towards glycopeptides. Furthermore, it also achieved outstanding performance in enriching glycopeptides from complex biological samples. In all, 273 glycopeptides corresponding to 94 glycoproteins were identified from only 2 μL human serum.
Pharmaceutical agents, drugs of abuse, and toxic substances have a large impact, positive and negative, on modern society. Efforts to mitigate the side effects of pharmaceuticals and counteract the ...life threatening effects of drugs of abuse and toxins can occur either by pharmacodynamic (PD) approaches based on bioreceptor·drug antagonism or by pharmacokinetic (PK) approaches that seek to reduce the concentration of free drug. In this tutorial review, we present the use of supramolecular hosts (cyclodextrins, calixarenes, (acyclic) cucurbiturils, and pillararenes) as in vivo sequestration agents for neuromuscular blockers, drugs of abuse (methamphetamine and fentanyl), anesthetics, neurotoxins, the pesticide paraquat, and heparin anti-coagulants by the PK approach. The review presents the basic physical and molecular recognition features of the supramolecular hosts and some of the principles used in their selection and structural optimization for in vivo sequestration applications. The influence of host·guest complexation on other relevant in vivo properties of drugs (e.g. distribution, circulation time, excretion, redox properties) is also mentioned. The article concludes with a discussion of future directions.
Metal-organic frameworks (MOFs) have been broadly applied to sample preparation which is an essential step in proteomics research. Their large surface area provides abundant binding sites, their ...specific pore structure can exclude large-sized proteins and allow small molecules to get inside their channels. Besides, the flexible functionalization gives infinite possibilities of MOFs applications in different fields including proteomics. In addition, the inherent metal centers and organic ligands endow them with strong affinities towards different target analytes. In this review, recent advances of MOFs in proteomics, containing separation of protein, enrichment of different types of peptides, glycan enrichment, etc., are extensively discussed. Besides, the MOFs as supports for enzyme immobilization and as matrixes and adsorbents for simultaneous separation and detection of peptides were also discussed detailedly. In the end, the outlook of synthesis and application of MOFs materials as well as existing challenges of MOFs in proteomics research are put forward.
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•Applications of metal-organic frameworks (MOFs) in protein separation are reviewed.•MOF-based materials for enrichment of peptides especially PTM peptides are comprehensively discussed.•Recent advances of MOF-based materials for glycan enrichment and enzyme immobilization are reported.•Performances of MOF-based materials as matrixes and adsorbents for small biomolecules are analyzed.•Other MOF-based applications in proteomics are mentioned.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
The molecular recognition properties of two pillarnarene sulfates (P5AS and P6AS) toward a panel of world anti-doping agency banned substances (1–11) were investigated by a combination of isothermal ...titration calorimetry, 1H NMR spectroscopy, and molecular modelling. Subsequently a sensing ensemble based on indicator displacement was created using the P5AS•lucigenin and P6AS•Hoechst 33258 complexes which allowed differentiation among the analytes with 90% accuracy. The assay was extended to allow the quantitation of pseudoephedrine in simulated urine samples with a limit of quantitation that is 30-fold below the WADA threshold.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Studies have explored the influence of DNA damage in assisted reproductive technology (ART), but the outcome remains controversial. To determine whether sperm DNA fragmentation index (DFI) has any ...effect on ART outcomes, we collected detailed data regarding 1,333 IVF cycles performed at our centre, and the data of our retrospective cohort study were extracted for this meta‐analysis. We searched PubMed, Web of Science, EMBASE and Google Scholar and performed a systemic review and meta‐analysis. Primary meta‐analysis of 10 studies comprising 1,785 couples showed that live birth rate was no significantly different between low‐DFI group and high‐DFI group (p > 0.05). Secondary meta‐analysis of 25 studies comprising 3,992 couples showed a higher miscarriage rate in high‐DFI group than in low‐DFI group (RR=1.57 1.18, 2.09, p < 0.01). Meta‐analysis of eight studies comprising 17,879 embryos revealed a lower good‐quality embryo rate (RR=0.65 0.62, 0.68, p < 0.01). Meta‐analysis of 23 studies comprising 6,771 cycles showed that the high‐DFI group had a lower clinical pregnancy rate than low‐DFI group (RR=0.85 0.75, 0.96, p < 0.01). Heterogeneity of included studies weakened our conclusions. Our study showed that DFI has adverse effects on ART outcome. More well‐designed studies exploring the association between DFI and ART outcome are desired.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Developing cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) has been the main tendency for low-abundance glycopeptides capture before LC-MS/MS analysis. ...Carbohydrates with outstanding biocompatibility and hydrophilicity are ubiquitous in the kingdoms of animal and plant and could be a wonderful choice as functional groups for glycopeptides enrichment. In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). Furthermore, the Fe3O4@G6P microspheres also exhibited enrichment ability for glycopeptides in different biosamples. A total of 243 glycopeptides assigned to 92 glycoproteins and 183 glycopeptides corresponding to 74 different glycoproteins was identified from merely 2 μL of serum and saliva, respectively.
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IJS, KILJ, NUK, PNG, UL, UM
We report an investigation of the complexation between a water soluble pillararene host (
WP6
) and a panel of hydrophobic cationic guests (
G1-G20
) by a combination of
1
H NMR spectroscopy and ...isothermal titration calorimetry in phosphate buffered saline. We find that
WP6
forms 1 : 1 complexes with
K
a
values in the 10
4
-10
9
M
−1
range driven by favorable enthalpic contributions. This thermodynamic dataset serves as blinded data for the SAMPL9 challenge.
We determined the thermodynamic parameters for a series of
WP6
·guest complexes as a blinded dataset for the SAMPL9 challenge.
Mitochondrial dysfunction and impaired Ca
handling are involved in the development of diabetic cardiomyopathy (DCM). Dynamic relative protein 1 (Drp1) regulates mitochondrial fission by changing its ...level of phosphorylation, and the Orai1 (Ca
release-activated calcium channel protein 1) calcium channel is important for the increase in Ca
entry into cardiomyocytes. We aimed to explore the mechanism of Drp1 and Orai1 in cardiomyocyte hypertrophy caused by high glucose (HG). We found that Zucker diabetic fat rats induced by administration of a high-fat diet develop cardiac hypertrophy and impaired cardiac function, accompanied by the activation of mitochondrial dynamics and calcium handling pathway-related proteins. Moreover, HG induces cardiomyocyte hypertrophy, accompanied by abnormal mitochondrial morphology and function, and increased Orai1-mediated Ca
influx. Mechanistically, the Drp1 inhibitor mitochondrial division inhibitor 1 (Mdivi-1) prevents cardiomyocyte hypertrophy induced by HG by reducing phosphorylation of Drp1 at serine 616 (S616) and increasing phosphorylation at S637. Inhibition of Orai1 with single guide RNA (sgOrai1) or an inhibitor (BTP2) not only suppressed Drp1 activity and calmodulin-binding catalytic subunit A (CnA) and phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) expression but also alleviated mitochondrial dysfunction and cardiomyocyte hypertrophy caused by HG. In addition, the CnA inhibitor cyclosporin A and p-ERK1/2 inhibitor U0126 improved HG-induced cardiomyocyte hypertrophy by promoting and inhibiting phosphorylation of Drp1 at S637 and S616, respectively. In summary, we identified Drp1 as a downstream target of Orai1-mediated Ca
entry, via activation by p-ERK1/2-mediated phosphorylation at S616 or CnA-mediated dephosphorylation at S637 in DCM. Thus, the Orai1-Drp1 axis is a novel target for treating DCM.
The (TiZrHfNbTaMo)C‐15 wt.% Co ceramics with excellent comprehensive properties were successfully prepared by vacuum liquid phase sintering. The effects of WC content on the grain size, ...microstructure, and mechanical properties were investigated. The results showed that WC was dissolved into (TiZrHfNbTaMo)C phase to form a seven‐component solid solution, and the independent WC phase disappeared. The addition of WC improved the wettability between the ceramic phase and the metal phase and promoted the densification of the ceramics. In addition, WC played a role in refining grains and inhibiting the grains growth to a certain extent. The comprehensive properties of ceramics were improved by solid solution strengthening and high entropy effect. When the WC content was 5 wt.%, the toughness reached the maximum of 9.41 ± 0.15 MPa·m1/2, and the hardness of the ceramic with 10 wt.% WC achieved the highest value of 18.18 ± 0.20 GPa.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Photoreceptor apoptosis is recognized as one key pathogenesis of retinal degeneration, the counteraction of which represents a promising approach to safeguard visual function. Recently, mesenchymal ...stem cell transplantation (MSCT) has demonstrated immense potential to treat ocular disorders, in which extracellular vesicles (EVs), particularly exosomes, have emerged as effective ophthalmological therapeutics. However, whether and how MSCT protects photoreceptors against apoptotic injuries remains largely unknown. Here, we discovered that intravitreal MSCT counteracted photoreceptor apoptosis and alleviated retinal morphological and functional degeneration in a mouse model of photoreceptor loss induced by N-methyl-N-nitrosourea (MNU). Interestingly, effects of MSCT were inhibited after blockade of exosomal generation by GW4869 preconditioning. Furthermore, MSC-derived exosomal transplantation (EXOT) effectively suppressed MNU-provoked photoreceptor injury. Notably, therapeutic efficacy of MSCT and EXOT on MNU-induced retinal degeneration was long-lasting as photoreceptor preservance and retinal maintenance were detected even after 1-2 months post to injection for only once. More importantly, using a natural occurring retinal degeneration model caused by a nonsense mutation of Phosphodiesterase 6b gene (Pde6b
), we confirmed that MSCT and EXOT prevented photoreceptor loss and protected long-term retinal function. In deciphering therapeutic mechanisms regarding potential exosome-mediated communications, we identified that miR-21 critically maintained photoreceptor viability against MNU injury by targeting programmed cell death 4 (Pdcd4) and was transferred from MSC-derived exosomes in vivo for functional regulation. Moreover, miR-21 deficiency aggravated MNU-driven retinal injury and was restrained by EXOT. Further experiments revealed that miR-21 mediated therapeutic effects of EXOT on MNU-induced photoreceptor apoptosis and retinal dysfunction. These findings uncovered the efficacy and mechanism of MSCT-based photoreceptor protection, indicating exosomal miR-21 as a therapeutic for retinal degeneration.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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