Click chemistry-based enrichment strategy for tracing cellular fatty acid metabolism by LC-MS/MS.

Fatty acids (FAs), which were initially recognized as energy sources and essential building blocks of biomembranes, serve as the precursors of important signaling molecules. Tracing FA metabolism is essential to understanding the biochemical activity and role of FAs in physiological and pathological events. Inspired by the advances in click chemistry for protein enrichment, we herein established a click chemistry-based enrichment (CCBE) strategy for tracing the cellular metabolism of eicosapentaenoic acid (EPA, 20:5 n-3) in neural cells. Terminal alkyne-labeled EPA (EPAA) used as a surrogate was incubated with N2a, mouse neuroblastoma cells, and alkyne-labeled metabolites (ALMs) were selectively captured by an azide-modified resin via a Cu(I)-catalyzed azide-alkyne cycloaddition reaction for enrichment. After removing unlabeled metabolites, ALMs containing a triazole moiety were cleaved from solid-phase resins and subjected to liquid chromatography mass spectrometry (LC-MS) analysis. The proposed CCBE strategy is highly selective for capturing and enriching alkyne-labeled metabolites from the complicated matrices. In addition, this method can overcome current detection limits by enhancing MS sensitivity of targets, improving the chromatographic separation of sn-position glycerophospholipid regioisomers, facilitating structural characterization of ALMs by a specific MS/MS fragmentation signature, and providing versatile fluorescence detection of ALMs for cellular distribution. This CCBE strategy might be expanded to trace the metabolism of other FAs, small molecules, or drugs.

THz enantiomers of drugs recognized by the polarization enhancement of gold nanoparticles on an asymmetric metasurface.

Chirality plays an important role in biological processes, and enantiomers often possess similar physical properties and different physiological functions. Thus, chiral detection of enantiomers has become a hot topic in recent years, and methods to enhance chiral molecular recognition are in urgent demand. In this work, a polarization detection method was used for different chiral drugs based on a specially designed metasurface composed of asymmetric double-opened rings and the surface enhancement effect of gold nanoparticles (GNPs). The experiment results show that the frequency shifts caused by the nearfield interaction of the metasurface and biomolecules have been significantly improved by GNPs, and both the limit of detection and detection precision of the metasurface can reach the 10-5 g ml-1 level. Moreover, the polarization sensing characterized by right circular polarization (RCP), the polarization elliptical angle (PEA), and the polarization rotation angle (PRA) shows that the enantiomers of three drugs can be distinguished, especially using the PEA spectrum; the maximum difference between enantiomers is over 30° with a precision of 6.6 × 10-7 g mL-1. Our THz polarization sensing and the GNP enhancement method inspire an efficient strategy for the highly sensitive detection of enantiomers.

Terahertz phase shift sensing and identification of a chiral amino acid based on a protein-modified metasurface through the isoelectric point and peptide bonding.

The efficient sensing of amino acids, especially the distinction of their chiral enantiomers, is important for biological, chemical, and pharmaceutical research. In this work, a THz phase shift sensing method was performed for amino acid detection based on a polarization-dependent electromagnetically induced transparency (EIT) metasurface. More importantly, a method for binding the specific amino acids to the functional proteins modified on the metasurface was developed based on the isoelectric point theory so that the specific recognition for Arginine (Arg) was achieved among the four different amino acids. The results show that via high-Q phase shift, the detection precision for L-Arg is 2.5 × 10-5 g /ml, much higher than traditional sensing parameters. Due to the specific electrostatic adsorption by the functionalized metasurface to L-Arg, its detection sensitivity and precision are 22 times higher than the other amino acids. Furthermore, by comparing nonfunctionalized and functionalized metasurfaces, the D- and L-chiral enantiomers of Arg were distinguished due to their different binding abilities to the functionalized metasurface. Therefore, this EIT metasurface sensor and its specific binding method improve both detection precision and specificity in THz sensing for amino acids, and it will promote the development of THz highly sensitive detection of chiral enantiomers.

Artificial intelligence: Emerging player in the diagnosis and treatment of digestive disease.

Given the breakthroughs in key technologies, such as image recognition, deep learning and neural networks, artificial intelligence (AI) continues to be increasingly developed, leading to closer and deeper integration with an increasingly data-, knowledge- and brain labor-intensive medical industry. As society continues to advance and individuals become more aware of their health needs, the problems associated with the aging of the population are receiving increasing attention, and there is an urgent demand for improving medical technology, prolonging human life and enhancing health. Digestive system diseases are the most common clinical diseases and are characterized by complex clinical manifestations and a general lack of obvious symptoms in the early stage. Such diseases are very difficult to diagnose and treat. In recent years, the incidence of diseases of the digestive system has increased. As AI applications in the field of health care continue to be developed, AI has begun playing an important role in the diagnosis and treatment of diseases of the digestive system. In this paper, the application of AI in assisted diagnosis and the application and prospects of AI in malignant and benign digestive system diseases are reviewed.

Selective modifications at the different positions of cyclodextrins: a review of strategies.

Cyclodextrins (CDs) are natural, nontoxic, and biodegradable macrocyclic oligosaccharides. As supramolecular hosts, CDs have numerous applications in many aspects. However, nonsubstituted CDs have the disadvantages of solubility, unspecific recognition sites, and weak interactions with guest molecules. Therefore, new CD-based derivatives are successfully designed, synthesized, and widely used in various fields. This contribution outlines the research progress in CD derivatives. In particular, this review emphasizes the synthesis and application of CDs modified through functionalization in definite positions, random substitution, and reconstruction of the skeleton. At the end of this review, a summary and future directions are presented.

[Factors associated with Th1 cytokine disorders in children with newly diagnosed type 1 diabetes].

OBJECTIVE: To measure levels of cytokines including IL-1ß, IL-12, IL-18 and TNF-α in children with newly diagnosed type 1 diabetes and to analyze their correlation with clinical indices such as infection and onset time. METHODS: A total of 33 children with newly diagnosed type 1 diabetes were assigned to the case group, and 27 healthy children to the control group. The case group was further divided into increased white blood cell (WBC) and normal WBC subgroups according to peripheral WBC level. The serum levels of cytokines including IL-1ß, IL-12, IL-18 and TNF-α were measured by enzyme-linked immunosorbent assay. Blood pH, blood sugar, blood lactate, fructosamine, peripheral leukocytes and neutrophils and some other clinical indices were also measured. RESULTS: The level of IL-12 in the case group was higher than in the control group (P<0.001). In the case group, the level of IL-18 was negatively correlated with onset time (r=0.413, P=0.015), the neutrophil count was positively correlated with IL-1ß level (r=0.413, P=0.023) and the WBC count was positively correlated with IL-18 level (r=0.352, P=0.038). IL-1ß, IL-12 and IL-18 levels in the increased WBC subgroup were higher than in the normal WBC subgroup (P<0.05 for all comparisons). CONCLUSIONS: Cytokine secretion disorders of Th1 cells exist in children with type 1 diabetes. Infections may induce cytokine secretion and might contribute to the early onset of diabetes.