In recent years, it has become a trend to employ organic molecular fluorescent probes with multireaction sites for the distinguishable detection and biological imaging of similar substances. However, the introduction of multireaction sites brought great challenges to organic synthesis, and at the same time, often destroyed the conjugated structure of the molecules, leading to an unsatisfactory fluorescence emission wavelength not conducive to practical application. As the eternal theme of life, metabolism goes on all the time. Metabolism is a series of ordered chemical reactions that occurs in the organism to maintain life. Chemical reactions in metabolism can be summarized as metabolic pathways. Simultaneous monitoring of different metabolic pathways of the same substance poses a lofty challenge to the probe. Here, we developed a new strategy: to construct new sites through the preliminary reactions between probes and some targets, which can be used to further distinguish among targets or detect their metabolites, so as to realize the simultaneous visualization tracer of multiple metabolic pathways. By intravenous injection, it revealed that the probe containing benzopyrylium ion can target tumors efficiently, and thiols are highly expressed in tumors compared to other tissues (heart, lung, kidney, liver, etc.). The consumption of thiols by the probe could not prevent tumor growth, suggesting that the tumor cure was not correlated with thiol concentration. The construction of new sites in the reaction process is a novel idea in the pursuit of multiple reaction sites, which will provide more effective tools for solving practical problems.

Chronic hepatitis C (CHC) is a major liver disease caused by the hepatitis C virus. The current standard of care for CHC can achieve cure rates above 95%; however, the drugs in current use are administered for a period of 8–16 weeks. A combination of safe and effective drugs with a shorter treatment period is highly desirable. We report synthesis and biological evaluation of a series of 2′,3′- and 2′,4′-substituted guanosine nucleotide analogues. Their triphosphates exhibited potent inhibition of the HCV NS5B polymerase with IC50 as low as 0.13 μM. In the HCV replicon assay, the phosphoramidate prodrugs of these analogues demonstrated excellent activity with EC50 values as low as 5 nM. A lead compound AL-611 showed high levels of the nucleoside 5′-triphosphate in vitro in primary human hepatocytes and in vivo in dog liver following oral administration.

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We report the synthesis and biological evaluation of a series of 4′-fluoro-2′-C-substituted uridines. Triphosphates of the uridine analogues exhibited a potent inhibition of hepatitis C virus (HCV) NS5B polymerase with IC50 values as low as 27 nM. In an HCV subgenomic replicon assay, the phosphoramidate prodrugs of these uridine analogues demonstrated a very potent activity with EC50 values as low as 20 nM. A lead compound AL-335 (53) demonstrated high levels of the nucleoside triphosphate in vitro in primary human hepatocytes and Huh-7 cells as well as in dog liver following a single oral dose. Compound 53 was selected for the clinical development where it showed promising results in phase 1 and 2 trials.

To enhance the advantage of a long-term stability and low-toxicity active packaging system, two biodegradable covalent immobilized antibacterial packaging films were developed and applied to fresh beef preservation in this study. A polylactic acid (PLA) film was prepared by the extrusion-casting method. The surface of the PLA film was modified with plasma treatment to generate carboxylic acid groups, and then antibacterial agent nisin or ε-poly lysine (ε-PL) was covalently attached to the modified film surface. Physical, chemical, and antimicrobial properties of films were then characterized. Scanning electron microscopy and water contact angle images confirmed that nisin or ε-PL was successfully grafted onto the film surface. The values of protein loading on the nisin−g−PLA film and ε-PL−g−PLA film were 5.34 ± 0.26 and 3.04 ± 0.25 μg of protein/cm 2 on the surface. Microbial analysis indicated that the grafted films effectively inhibit the growth of bacteria. Finally, the effects of the nisin−g−PLA film or ε-PL−g−PLA film on physicochemical changes and microbiological counts of fresh beef during cold storage at 4 °C were investigated. The total viable count of the control sample exceeded 7 logarithms of the number of colony forming units per gram (log CFU/g) after 11 days of cold storage (7.01 ± 0.14 log CFU/g) versus 15 days for the ε-PL−g−PLA film (7.37 ± 0.06 log CFU/g) and the nisin−g−PLA film (6.83 ± 0.10 log CFU/g). The results showed that covalent immobilized antibacterial packaging films had positive impacts on the shelf life and quality of fresh beef. Therefore, a covalent immobilized antibacterial packaging system could be a novel preservative method for foods.