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Derived from the D‐luciferin regeneration pathway in firefly body, the click condensation reaction between 2‐cyanobenzothiazole (CBT) and D‐cysteine (Cys) (CBT‐Cys click reaction) possesses unique advantages, including superior biocompatibility, high second order reaction rate, and metal‐free mild conditions, emerging as a powerful bioorthogonal tool for a variety of chemical biological applications. Moreover, owing to its programmable controllability (e.g., pH, reduction, or enzyme), CBT‐Cys click reaction is exploited to fabricate stimuli‐activatable imaging probes with self‐assembling behaviors in physiological context. At stimuli‐rich pathological lesions of interest, these probes undergo CBT‐Cys click reaction to form cyclic dimers/oligomers or linear polymers, and further self‐assemble into nanostructures. The in situ formed nanostructures promote the selective accumulation and retention of imaging agent cargos at pathological lesions, thus enabling precise and enhanced in vivo imaging of diseases (especially tumors). To address the significance and recent breakthroughs of smart CBT‐Cys probes for enhanced optical imaging of tumors/other diseases, we herein propose this mini‐review, in which advances (particularly in recent 5 years) and potential challenges (or chances) in this field are emphasized. [ABSTRACT FROM AUTHOR]

Azide-alkyne cycloaddition reaction is a very common organic reaction to synthesize nitrogen-containing heterocycles. Once catalyzed by Cu(I) or Ru(II), it turns out to be a click reaction and thus is widely applied in chemical biology for labeling. However, besides their poor regioselectivity towards this reaction, these metal ions are not biologically friendly. Hence, it is an urgent need to develop a metal-free azide–alkyne cycloaddition reaction for biomedical applications. In this work, we found that, in the absence of metal ions, supramolecular self-assembly in an aqueous solution could realize this reaction with excellent regioselectivity. Nap-Phe-Phe-Lys(azido)-OH firstly self-assembled into nanofibers. Then, Nap-Phe-Phe-Gly(alkynyl)-OH at equivalent concentration approached to react with the assembly to yield the cycloaddition product Nap-Phe-Phe-Lys(triazole)-Gly-Phe-Phe-Nap to form nanoribbons. Due to space confinement effect, the product was obtained with excellent regioselectivity. Employing the excellent properties of supramolecular self-assembly, we are applying this strategy to realize more reactions without metal ion catalysis. Metal-free versions of azide–alkyne cycloadditions could find widespread applications in biomedical contexts. Here, the authors report an assembly-driven, regioselective azide–alkyne cycloaddition. [ABSTRACT FROM AUTHOR]

Abstract: The dysregulation of NLRP3 inflammasome can cause uncontrolled inflammation and drive the development of a wide variety of human diseases, but the medications targeting NLRP3 inflammasome are not available in clinic. Here, we show that tranilast (TR), an old anti‐allergic clinical drug, is a direct NLRP3 inhibitor. TR inhibits NLRP3 inflammasome activation in macrophages, but has no effects on AIM2 or NLRC4 inflammasome activation. Mechanismly, TR directly binds to the NACHT domain of NLRP3 and suppresses the assembly of NLRP3 inflammasome by blocking NLRP3 oligomerization. In vivo experiments show that TR has remarkable preventive or therapeutic effects on the mouse models of NLRP3 inflammasome‐related human diseases, including gouty arthritis, cryopyrin‐associated autoinflammatory syndromes, and type 2 diabetes. Furthermore, TR is active ex vivo for synovial fluid mononuclear cells from patients with gout. Thus, our study identifies the old drug TR as a direct NLRP3 inhibitor and provides a potentially practical pharmacological approach for treating NLRP3‐driven diseases. [ABSTRACT FROM AUTHOR]

Background : Nowadays, magnetic resonance imaging (MRI) is routinely applied in clinical diagnosis. However, using one contrast agent (CA) to simultaneously enhance the T 1 and T 2 MR contrast at low and high magnetic fields respectively has not been reported. Methods : Herein, we investigated the MR property of a γ-glutamyl transpeptidase (GGT)-instructed, intracellular formed gadolinium nanoparticle (DOTA-Gd-CBT-NP) at low and high magnetic fields. Results : Experimental results showed that DOTA-Gd-CBT-NP possesses a low r 2 /r 1 ratio 0.91 which enables it to enhance T 1 MR imaging of liver tumor at 1.0 T, and a high r 2 /r 1 ratio 11.8 which renders the nanoparticle to largely enhance T 2 MR imaging of liver tumor at 9.4 T. Conclusion: We expect that our GGT-responsive Gd-nanoparticle could be applied for simultaneous T 1 and T 2 MRI diagnosis of early liver cancer in clinic at respective low and high magnetic fields when the 9.4 T MR machine is clinically available in the future., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)