Design, synthesis and biological evaluation of novel 3,4-dihydro-2H-[1,4]oxazino [2,3-f]quinazolin derivatives as EGFR-TKIs.

Starting with our previously reported work, a novel series of 3,4-dihydro-2H-[1,4]oxazino[2,3-f]quinazolin-derivatives were designed, synthesized and evaluated as potent EGFR tyrosine kinase inhibitors. All of the compounds showed significant inhibitory activities against EGFRwt kinase (IC50 ≤ 937.7 nM). Among them, compound 7j demonstrated the most potent inhibitory activity toward EGFRwt tyrosine kinase with IC50 value of 25.69 nM and showed good antiproliferative activities against NCI-H1563 and H1975 cells. The median cytotoxic concentration (CC50) showed that most of the tested compounds displayed almost no cytotoxicity in vitro against 16HBE cells. In view of the reported compounds activity, the structure deserves further optimization as cancer treatment agents.

A ferrocene-based multiple-stimuli responsive organometallogel.

Three new ferrocene-peptide compounds were designed and prepared. We investigated their gelling abilities and found that two of them were capable of gelling various organic solvents, especially alcohols. Gels also formed in mixed alcohol-water solvents, which decreased the critical gelation concentration (CGC) of the gels. Compound 1, comprised of a dipeptide (Phe-Phe) and ferrocene, acted as a novel low-molecular-weight gelator in the formation of metallogel 1 in isopropanol-water (v/v = 1 : 1). This gelation was found to be reversible under redox stimuli; changing of the redox state of ferrocene induced a reversible gel-sol phase transition. Additionally, gel 1 responded to ß-CD as a result of host-guest interactions between this compound and ferrocene. With the addition of ß-CD, the gel network gradually broke down, as demonstrated by SEM.

A selenium-contained aggregation-induced "turn-on" fluorescent probe for hydrogen peroxide.

A selenium-contained fluorescent 'turn-on' probe D-HMSe was developed for monitoring hydrogen peroxide. The probe D-HMSe is highly selective to hydrogen peroxide over other reactive oxygen species (ROS). An aggregation-induced enhancement (AIE) phenomenon was involved in the sensing process.

Synthesis, characterization, DFT studies, and adsorption properties of sulfonated starch synthesized in deep eutectic solvent.

In this study, sulfonated starch (SS) was successfully synthesized using sulfamic acid as a sulfonating agent in a deep eutectic solvent (DES). Four-factor and three-level orthogonal experiments were conducted to determine the optimal preparation conditions, which were found to be a molar ratio of starch to urea of 1:20, a reaction temperature of 90 °C, a reaction time of 5 h, and a stirring speed of 200 rpm. The sulfonation reaction mechanism was extensively studied using various techniques, including Fourier transform infrared spectroscopy, elemental analysis, X-ray diffraction, molecular weight, particle distribution, X-ray photoelectron spectroscopy, scanning electron microscopy, and DFT calculations. The results showed that the sulfonation reaction slightly damaged starch granules, occurred on the surface of starch granules, and on the O6 atoms of the glucose unit. SS exhibited a wide pH range of application (5-10), a fast adsorption rate (400 s to reach adsorption equilibrium), and a high adsorption capacity (118.3 mg/g) under optimal conditions. The adsorption process of SS for methylene blue followed the pseudo-first-order kinetic model and was consistent with the Langmuir model, which was endothermic and spontaneous. The adsorption process was attributed to hydrogen bonding and electrostatic interactions.

In situ embedding of glucose oxidase in amorphous ZIF-7 with high catalytic activity and stability and mechanism investigation.

Glucose oxidase (GOx) has a great application potential in the determination of glucose concentration. However, its sensitivity to the environment and poor recyclability limited its broader application. Herein, with the assistance of DA-PEG-DA, a novel immobilized GOx based on amorphous Zn-MOFs (DA-PEG-DA/GOx@aZIF-7/PDA) was developed to impart excellent properties to the enzyme. SEM, TEM, XRD, and BET analyses confirmed that GOx was embedded in amorphous ZIF-7 with ∼5 wt% loading. Compared with free GOx, DA-PEG-DA/GOx@aZIF-7/PDA exhibited enhanced stability, excellent reusability, and promising potential for glucose detection. After 10 repetitions, the catalytic activity of DA-PEG-DA/GOx@aZIF-7/PDA can maintain 95.53 % ± 3.16 %. In understanding the in situ embedding of GOx in ZIF-7, the interaction of zinc ion and benzimidazole with GOx was studied by using molecular docking and multi-spectral methods. Results showed that zinc ions and benzimidazole had multiple binding sites on the enzyme, which induced the accelerated synthesis of ZIF-7 around the enzyme. During binding, the structure of the enzyme changes, but such changes hardly affect the activity of the enzyme. This study provides not only a preparation strategy of immobilized enzyme with high activity, high stability, and low enzyme leakage rate for glucose detection, but also a more comprehensive understanding of the formation of immobilized enzymes using the in situ embedding strategy.

Fluorescence Imaging of Diabetic Cataract-Associated Lipid Droplets in Living Cells and Patient-Derived Tissues.

Diabetic cataract (DC) surgery carries risks such as slow wound healing, macular edema, and progression of retinopathy and is faced with a deficiency of effective drugs. In this context, we proposed a protocol to evaluate the drug's efficacy using lipid droplets (LDs) as the marker. For this purpose, a fluorescent probe PTZ-LD for LDs detection is developed based on the phenothiazine unit. The probe displays polarity-dependent emission variations, i.e., lower polarity leading to stronger intensity. Especially, the probe exhibits photostability superior to that of Nile Red, a commercial LDs staining dye. Using the probe, the formation of LDs in DC-modeled human lens epithelial (HLE) cells is validated, and the interplay of LDs-LDs and LDs-others are investigated. Unexpectedly, lipid transfer between LDs is visualized. Moreover, the therapeutic efficacy of various drugs in DC-modeled HLE cells is assessed. Ultimately, more LDs were found in lens epithelial tissues from DC patients than in cataract tissues for the first time. We anticipate that this work can attract more attention to the important roles of LDs during DC progression.

Novel CaCO3/chitin aerogel: Synthesis and adsorption performance toward Congo red in aqueous solutions.

In this study, chitin aerogel doped with nano-calcium carbonate (CaCO3/chitin aerogel) was prepared by dissolving chitin in Na2CO3/Ca (OH)2/urea system followed by epichlorohydrin (ECH) addition as a cross-linker and then freeze-drying of the hydrogel. The as-obtained CaCO3/chitin aerogel showed good adsorption properties toward the adsorption of Congo Red (CR) with maximum adsorption capacity reaching approximately 266.4 mg·g-1. Besides, the adsorption capacity was affected by the initial concentration and pH. The adsorption kinetics revealed a second-order kinetics model of CaCO3/chitin aerogel toward CR, and the adsorption process was controlled by both the liquid film diffusion and intra-particle diffusion. In sum, chitin aerogel looks promising as an effective adsorbent for anion dye adsorption. The cost-effective and eco-friendly developed approaches are also of great interest for future environmental remediation.

In-situ preparation of biochar-loaded particle electrode and its application in the electrochemical degradation of 4-chlorophenol in wastewater.

In order to effectively degrade 4-chlorophenol in wastewater, a biochar-loaded particle electrode was prepared using an in-situ method. The method employed bagasse as the raw material, KOH as the activator, SnCl4·5H2O, MnCl2·4H2O and SbCl3 as the modifiers. Furthermore, X-ray diffraction, scanning electron microscopy and energy dispersive spectrometer were used to characterize the crystal composition, morphology and elemental compositions of the proposed particle electrode. The electrochemical performance of the proposed particle electrode was analyzed using an electrochemical workstation. A three-dimensional packed-bed electrochemical reactor was constructed using the loaded biomass carbon particle electrodes. The effects of different loaded biomass carbon particle electrodes on the electrochemical degradation of 4-chlorophenol were studied, and the mechanism of electrochemical degradation of 4-chlorophenol was discussed. The results showed that the effect of the supported biomass carbon particle electrode on the degradation of 4-chlorophenol was significantly higher than that of the unsupported biomass carbon particle electrode. Additionally, the electrochemical degradation of 4-chlorophenol was greatly influenced by the biomass carbon particle electrode with different loading and concentration. The removal efficiencies of 4-chlorophenol using the electrochemical treatment under the studied experimental conditions were found in the following descending order: Mn/AC > Sn/AC > Sb/AC. Among them, the biomass carbon particle electrode prepared using 150 g L-1 MnCl2·4H2O showed the best treatment effect for 4-chlorophenol. After electrochemical treatment of 500 mg L-1 of 4-chlorophenol-simulated wastewater for 1 h, the removal efficiency of 4-chlorophenol reached 99.93%.

A ratiometric fluorescent probe for in situ quantification of basal mitochondrial hypochlorite in cancer cells.

A ratiometric fluorescent probe () for ClO(-) based on the conjugate of coumarin-rhodamine was presented, which could sense ClO(-) with fast response (within 5 s), high sensitivity and excellent selectivity. More importantly, is the first mitochondria-targeted ratiometric fluorescent probe to image exogenous and endogenous ClO(-).

A highly selective water-soluble optical probe for endogenous peroxynitrite.

A colorimetric and fluorescent probe C-Py-1 for ONOO(-) was prepared and it could exhibit high sensitivity and excellent selectivity toward ONOO(-) among reactive oxygen species (ROS) and reactive nitrogen species (RNS) with a rapid response time in 100% water solution. Meanwhile, C-Py-1 was successfully applied in the imaging of endogenous ONOO(-) in RAW264.7 cells.