A near-infrared hepatocyte-targeting probe based on Tricyanofuran to detect cysteine in vivo: Design, synthesis and evaluation.

In this work, a near-infrared hepatocyte-targeting fluorescence probe TCF-Gal-Cys was developed. The TCF-Gal-Cys exhibited a low detection limit, good sensitivity and selectivity toward Cys. The responsive mechanism of TCF-Gal-Cys was proposed that the acrylate of TCF-Gal-Cys was subsequently attacked by the thiol group and the amino group of Cys, releasing a strong near-infrared fluorescent group. TCF-Gal-Cys displayed a good hepatocyte-targeting capacity and could specifically distinguish hepatocytes from A549, Hela, SGC-7901 cells because the galactose group of TCF-Gal-Cys can be recognized by HepG2 cells overexpressing ASGPR. The TCF-Gal-Cys has achieved excellently imaging performance to Cys in the zebrafish, so TCF-Gal-Cys has potential to be an effective tool to in real time monitor Cys-related diseases in vitro and in vivo.

Interaction between ABA and NO in plants under abiotic stresses and its regulatory mechanisms.

Abscisic acid (ABA) and nitric oxide (NO), as unique signaling molecules, are involved in plant growth, developmental processes, and abiotic stresses. However, the interaction between ABA and NO under abiotic stresses has little been worked out at present. Therefore, this paper reviews the mechanisms of crosstalk between ABA and NO in the regulation of plants in response to environmental stresses. Firstly, ABA-NO interaction can alleviate the changes of plant morphological indexes damaged by abiotic stresses, for instance, root length, leaf area, and fresh weight. Secondly, regulatory mechanisms of interaction between ABA and NO are also summarized, such as reactive oxygen species (ROS), antioxidant enzymes, proline, flavonoids, polyamines (PAs), ascorbate-glutathione cycle, water balance, photosynthetic, stomatal movement, and post-translational modifications. Meanwhile, the relationships between ABA and NO are established. ABA regulates NO through ROS at the physiological level during the regulatory processes. At the molecular level, NO counteracts ABA through mediating post-translational modifications. Moreover, we also discuss key genes related to the antioxidant enzymes, PAs biosynthesis, ABA receptor, NO biosynthesis, and flavonoid biosynthesis that are regulated by the interaction between ABA and NO under environmental stresses. This review will provide new guiding directions for the mechanism of the crosstalk between ABA and NO to alleviate abiotic stresses.

Two Fluorescent Probes for Recognition of Acetylcholinesterase: Design, Synthesis, and Comparative Evaluation.

In this study, two "on-off" probes (BF2-cur-Ben and BF2-cur-But) recognizing acetylcholinesterase (AChE) were designed and synthesized. The obtained probes can achieve recognition of AChE with good selectivity and pH-independence with a linear range of 0.5~7 U/mL and 0.5~25 U/mL respectively. BF2-cur-Ben has a lower limit of detection (LOD) (0.031 U/mL), higher enzyme affinity (Km = 16 ± 1.6 µM), and higher inhibitor sensitivity. A responsive mechanism of the probes for AChE was proposed based on HPLC and mass spectra (MS) experiments, as well as calculations. In molecular simulation, BF2-cur-Ben forms more hydrogen bonds (seven, while BF2-cur-But has only four) and thus has a more stable enzyme affinity, which is mirrored by the results of the comparison of Km values. These two probes could enable recognition of intracellular AChE and probe BF2-cur-Ben has superior cell membrane penetration due to its higher log p value. These probes can monitor the overexpression of AChE during apoptosis of lung cancer cells. The ability of BF2-cur-Ben to monitor AChE in vivo was confirmed by a zebrafish experiment.

Design, synthesis, and evaluation of a carboxylesterase detection probe with therapeutic effects.

In this study, a lysosomal targeting fluorescent probe recognition on CEs was designed and synthesized. The obtained probe BF2-cur-Mor demonstrated excellent selectivity, sensitivity, pH-independence, and enzyme affinity towards CEs within 5 min. BF2-cur-Mor could enable recognition of intracellular CEs and elucidate that the CEs content of different cancer cells follows the rule of HepG2 > HCT-116 > A549 > HeLa, and the CEs expression level of hepatoma cancer cells far exceeds that of normal hepatic cells, being in good agreement with the previous reports. The ability of BF2-cur-Mor to monitor CEs in vivo was confirmed by zebrafish experiment. BF2-cur-Mor exhibits some pharmacological activity in that it can induce apoptosis in hepatocellular carcinoma cells but is weaker in normal hepatocyte cells, being expected to be a potential "diagnostic and therapeutic integration" tool for the clinical diagnosis of CEs-related diseases.

Progress of metal nanoclusters in nucleic acid detection.

The development and application of metal nanoclusters (MNCs) in nucleic acid testing in the past 10 years have been summarized. Fluorescence enhancement and red shift can occur when the G-rich sequence gets close to Ag NCs or the complementary DNA strand hybridizes with Ag NCs tail strand, which can be used to identify the nucleic acid. Ag NCs with the abasic site in DNA duplex can distinguish mutant genes such as cancer suppression gene p53. Ag NCs with auxiliary DNA can be used to detect miR-21, miR-16-5p, miR-19b-3p, and miR-141. Cu NCs/Cu NPs can recognize miRNA-155, miR-21, and miR-let-7d without auxiliary DNA. Au NCs can identify H1N1 gene fragments by fluorescence quenching caused by proximity to the G-rich sequence. Besides, Au NCs can recognize miRNA-21 and let-7a. SsDNA MNCs adsorbed on the surface of GO and CNPs oxide can be used to identify HBV and HIV gene fragments. The addition of enzymes or auxiliary amplification technologies is a popular way to improve probe sensitivity. Ag NCs combined with TAIEA has the best performance and can obtain LOD as low as aM for miRNA.

Advance of structural modification of nucleosides scaffold.

With Remdesivir being approved by FDA as a drug for the treatment of Corona Virus Disease 2019 (COVID-19), nucleoside drugs have once again received widespread attention in the medical community. Herein, we summarized modification of traditional nucleoside framework (sugar + base), traizole nucleosides, nucleoside analogues assembled by other drugs, macromolecule-modified nucleosides, and their bioactivity rules. 2'-"Ara"-substituted by -F or -CN group, and 3'-"ara" substituted by acetylenyl group can greatly influence their anti-tumor activities. Dideoxy dehydrogenation of 2',3'-sites can enhance antiviral efficiencies. Acyclic nucleosides and L-type nucleosides mainly represented antiviral capabilities. 5-F Substituted uracil analogues exihibit anti-tumor effects, and the substrates substituted by -I, -CF3, bromovinyl group usually show antiviral activities. The sugar coupled with 1-N of triazolid usually displays anti-tumor efficiencies, while the sugar coupled with 2-N of triazolid mainly represents antiviral activities. The nucleoside analogues assembled by cholesterol, polyethylene glycol, fatty acid and phospholipid would improve their bioavailabilities and bioactivities, or reduce their toxicities.