An activatable near-infrared fluorescent probe with large Stokes shift for visualizing peroxynitrite in Alzheimer's disease models.

Alzheimer's disease (AD), characterized by its incurable nature and prevalence among the elderly, has remained a focal point in medical research. Increasing evidence suggests that peroxynitrite (ONOO-) serves as a crucial biomarker for the diagnosis of AD. In this study, we present a novel, easily available, high-yield, and cost-effective near-infrared (NIR) fluorescent probe, CDCI-ONOO. This probe utilizes a coumarin-dicyanoisophorone conjugate as the fluorophore and diphenylphosphinic chloride as the recognition site, enabling the detection of ONOO- both in vitro and in vivo. Upon interaction with ONOO-, CDCI-ONOO exhibits a distinct maximum emission peak at 715 nm with a substantial Stokes shift of 184 nm. The probe demonstrates excellent selectivity and sensitivity (LOD = 144 nM), along with noticeable colorimetric and fluorescence changes after the reaction. Comprehensive analyses using high-performance liquid chromatography (HPLC), high-resolution mass spectrometry (HRMS), and density functional theory (DFT) calculations confirm that the reaction with ONOO- restores the initially quenched Intramolecular Charge Transfer (ICT), resulting in the formation of CDCI-OH, a product that emitting fluorescence in the near-infrared region. Furthermore, we demonstrated the successful application of CDCI-ONOO for ONOO- detection in neuronal cells and imaging of ONOO- in the brains of mice. These findings underscore the potential of CDCI-ONOO as a near-infrared fluorescent probe for in vivo ONOO- detection, offering a significant avenue for advancing our understanding of AD pathology and diagnosis.

A Near-Infrared Fluorescent Probe with Large Stokes Shift for Sensitive Detection of Hydrogen Sulfide in Environmental Water, Food Spoilage, and Biological Systems.

Hydrogen sulfide (H2S) is an important endogenous gas transmitter that plays a critical role in various physiological and pathological processes and can also cause a negative impact on foodstuffs. In this study, we designed and synthesized a simple, easily available, high-yield, and low-cost near-infrared (λem = 710 nm) fluorescent probe, DEM-H2S, with a substantial Stokes shift (205 nm) for the detection of H2S. DEM-H2S features high selectivity and sensitivity (LOD = 80 nM) toward H2S, accompanied by a noticeable color change. Upon interaction with H2S, DEM-H2S exhibits a restored ICT (Intramolecular Charge Transfer) process, thereby manifesting near-infrared fluorescence. DEM-H2S has been successfully utilized to detect H2S in actual water samples and to monitor the spoilage of food items, such as pork, shrimp, and eggs. Furthermore, DEM-H2S enables the imaging of endogenous and exogenous H2S in living MCF-7 cells and zebrafish. Hence, DEM-H2S provides an attractive method for the detection of H2S in environmental, food, and biological systems, holding potential value in physiological and pathological research.

Biological evaluation and SAR analysis of novel covalent inhibitors against fructose-1,6-bisphosphatase.

Fructose-1,6-bisphosphatase (FBPase) is an attractive target for affecting the GNG pathway. In our previous study, the C128 site of FBPase has been identified as a new allosteric site, where several nitrovinyl compounds can bind to inhibit FBPase activity. Herein, a series of nitrostyrene derivatives were further synthesized, and their inhibitory activities against FBPase were investigated in vitro. Most of the prepared nitrostyrene compounds exhibit potent FBPase inhibition (IC50 < 10 µM). Specifically, when the substituents of F, Cl, OCH3, CF3, OH, COOH, or 2-nitrovinyl were installed at the R2 (meta-) position of the benzene ring, the FBPase inhibitory activities of the resulting compounds increased 4.5-55 folds compared to those compounds with the same groups at the R1 (para-) position. In addition, the preferred substituents at the R3 position were Cl or Br, thus compound HS36 exhibited the most potent inhibitory activity (IC50 = 0.15 µM). The molecular docking and site-directed mutation suggest that C128 and N125 are essential for the binding of HS36 and FBPase, which is consistent with the C128-N125-S123 allosteric inhibition mechanism. The reaction enthalpy calculations show that the order of the reactions of compounds with thiol groups at the R3 position is Cl > H > CH3. CoMSIA analysis is consistent with our proposed binding mode. The effect of compounds HS12 and HS36 on glucose production in primary mouse hepatocytes were further evaluated, showing that the inhibition was 71% and 41% at 100 µM, respectively.

Multifunctional Mineral Hydrogels: Potential in Artificially Intelligent Skins and Drug Delivery.

Hydrogels have received considerable attention due to their potential applications in the fields of drug delivery, tissue engineering, and stimuli-responsive devices. Nonetheless, it is still a great difficulty in designing hydrogels with multifunctional characteristics including excellent antibacterial activity and appropriate mechanical and remarkable sensing properties. In the present study, a novel type of organic-inorganic adhesive is demonstrated, which comprises inorganic matter of amorphous calcium phosphate particles and organic substances of poly(acrylic acid) and chitosan. The hydrogel possesses excellent biocompatible and antibacterial activity, unique viscoelastic properties, high quantity of drug load, and remarkably sensitive pressure sensing, which have potential use as antibacterial biomaterials, artificially intelligent skins, and drug delivery carriers.

Investigation of genetic diversity of the bla(SHV) gene and development of an oligonucleotide microarray to detect mutations in the bla(SHV) gene.

SHV ß-lactamases, including SHV extended-spectrum ß-lactamases, are widespread throughout the world, and confer a broad spectrum of resistance to antibiotic drugs. Mutations ranging from single base-pair substitutions to small deletions within bla(SHV) often result in diminished activity and an increased susceptibility to ß-lactamase inhibitors. Here, we collected 1,320 clinical isolates from three hospitals in Shanghai. We developed a novel oligonucleotide microarray to detect mutations in the bla(SHV) gene, and validated the array data by direct sequencing. Sixty-two of the 1,320 isolates carried the bla(SHV) gene. The genotypes of these 62 isolates were successfully called by the microarray and were consistent with the genotypes identified by bidirectional sequencing. Sixteen different bla(SHV) alleles were identified. The SHV-1 variant was the most frequent (32.26%), followed by SHV-11 (27.42%) and SHV-12 (25.81%). Of the 62 isolates, 12 contained two different bla(SHV) alleles. Our microarray significantly facilitated the identification of bla(SHV) variants, which makes it an attractive option for the detection of SHV variants in clinical laboratories.