Discovery of Novel Coumarin-quinolinium Derivatives as Pan-KRAS Translation Inhibitors by Targeting 5'-UTR RNA G-Quadruplexes.

Hyperactivated KRAS mutations fuel tumorigenesis and represent attractive targets for cancer treatment. While covalent inhibitors have shown clinical benefits against the KRASG12C mutant, advancements for non-G12C mutants remain limited, highlighting the urgent demand for pan-KRAS inhibitors. RNA G-quadruplexes (rG4s) in the 5'-untranslated region of KRAS mRNA can regulate KRAS translation, making them promising targets for pan-KRAS inhibitor development. Herein, we designed and synthesized 50 novel coumarin-quinolinium derivatives, leveraging our previously developed rG4-specific ligand, QUMA-1. Notably, several compounds exhibited potent antiproliferative activity against cancer cells as pan-KRAS translation inhibitors. Among them, 15a displayed exceptional capability in stabilizing KRAS rG4s, suppressing KRAS translation, and consequently modulating MAPK and PI3K-AKT pathways. 15a induced cell cycle arrest, prompted apoptosis in KRAS-driven cancer cells, and effectively inhibited tumor growth in a KRAS mutant xenograft model. These findings underscore the potential of 15a as a pan-KRAS translation inhibitor, offering a novel and promising approach to target various KRAS-driven cancers.

Revealing Mitochondrion-Lysosome Dynamic Interactions and pH Variations in Live Cells with a pH-Sensitive Fluorescent Probe.

Mitochondrion-lysosome interactions have garnered significant attention in recent research. Numerous studies have shown that mitochondrion-lysosome interactions, including mitochondrion-lysosome contact (MLC) and mitophagy, are involved in various biological processes and pathological conditions. Single fluorescent probes are termed a pivotal chemical tool in unraveling the intricate spatiotemporal interorganelle interplay in live cells. However, current chemical tools are insufficient to deeply understand mitochondrion-lysosome dynamic interactions and related diseases, Moreover, the rational design of mitochondrion-lysosome dual-targeting fluorescent probes is intractable. Herein, we designed and synthesized a pH-sensitive fluorescent probe called INSA, which could simultaneously light up mitochondria (red emission) and lysosomes (green emission) for their internal pH differences. Employing INSA, we successfully recorded long-term dynamic interactions between lysosomes and mitochondria. More importantly, the increasing mitochondrion-lysosome interactions in ferroptotic cells were also revealed by INSA. Further, we observed pH variations in mitochondria and lysosomes during ferroptosis for the first time. In brief, this work not only introduced a pH-sensitive fluorescent probe INSA for the disclosure of the mitochondrion-lysosome dynamic interplays but also pioneered the visualization of the organellar pH alternation in a specific disease model.

The impact of different drying methods on the physical properties, bioactive components, antioxidant capacity, volatile components and industrial application of coffee peel.

This study evaluated the effects of hot air drying (HAD), microwave drying (MD), vacuum drying (VD), sun drying (SD) and vacuum freeze drying (VFD) on the physical properties, bioactive components, antioxidant capacity, volatile components and industrial application of coffee peel. The results showed VFD could retain the appearance color, total phenolics (19.49 mg GAE/g DW), total flavonoids (9.65 mg CE/g DW), caffeine (3.15 mg/g DW), trigonelline (2.71 mg/g DW), and antioxidant capacities of fresh sample to the greatest extent, but its operating cost was significantly higher than other treatments and total volatile components were in the minimum levels. HAD and SD exhibited the highest loss rates of total phenols and antioxidant capacities, exceeding 50%. MD offered the lowest operating cost, superior retention of bioactive components, and the richest variety and quantity of volatile compounds. Therefore, it is recommended to use MD to dehydrate the coffee peel in actual production.

Bioinspired Thermochromic Textile Based on Robust Cellulose Aerogel Fiber for Self-Adaptive Thermal Management and Dynamic Labels.

Aerogel fiber has emerged recently for incorporation in personal thermal management textiles due to its flexibility, scalability, and ultrahigh porosity, which allows the body to keep warm via thermal isolation without energy consumption. However, the functionalization and intellectualization of cellulose-based aerogel fibers have not yet been fully developed. Herein, we propose a biomimicking design inspired by polar bear and Siamese cat hair that combines porous cellulose aerogel fiber (CAF) with reversible thermochromic microcapsules to mimic biological sensory and adaptive thermoregulation functions. The produced CAF has a controllable pore structure, a large specific surface area (230 m2/g), and excellent mechanical strength (∼15 MPa). Low-temperature darkening microcapsules have been incorporated into the robust CAF to spontaneously adjust color by perceiving the ambient temperature. The functional aerogel fiber fabric achieves high thermal insulation and photothermal modulation simultaneously at temperatures below 18 °C. The temperature of the thermochromic fabric was higher by 6 °C than that of the sample without the microcapsules at a light intensity of 0.2 W/cm2. In addition, the aerogel fibers mixed with two types of thermochromic microcapsules exhibit three color switches with fast response, a color-control precision of 0.2 °C, and good cycling performance. This smart aerogel fibers hold great promise for self-adaptive thermal management, temperature indication, information transfer, and anticounterfeiting in textiles.

Development of Smart Films of a Chitosan Base and Robusta Coffee Peel Extract for Monitoring the Fermentation Process of Pickles.

Smart film is widely used in the field of food packaging. The smart film was prepared by adding anthocyanin-rich Robusta coffee peel (RCP) extract into a chitosan (CS)-glycerol (GL) matrix by a solution-casting method. By changing the content of RCP (0, 10%, 15% and 20%) in the CS-GL film, the related performance indicators of CS-GL-RCP films were studied. The results showed that the CS-GL-RCP films had excellent mechanical properties, and CS-GL-RCP15 film maintained the tensile strength (TS) of 16.69 MPa and an elongation-at-break (EAB) of 18.68% with RCP extract. CS-GL-RCP films had the best UV-vis light barrier property at 200-350 nm and the UV transmittance was close to 0. The microstructure observation results showed that CS-GL-RCP films had a dense and uniform cross section, which proved that the RCP extract had good compatibility with the polymer. In addition, the CS-GL-RCP15 film was pH-sensitive and could exhibit different color changes with different pH solutions. So, the CS-GL-RCP15 film was used to detect the fermentation process of pickles at 20 ± 1 °C for 15 days. The pickles were stored in a round pickle container after the boiling water had cooled. The color of the CS-GL-RCP15 film changed significantly, which was consistent with the change of pickles from fresh to mature. The color of the smart film changed significantly with the maturity of pickles, and the difference of ΔE of film increased to 8.89 (15 Days), which can be seen by the naked eye. Therefore, CS-GL-RCP films prepared in this study provided a new strategy for the development of smart packaging materials.

Development of a Highly Selective and Sensitive Fluorescent Probe for Imaging RNA Dynamics in Live Cells.

RNA imaging is of great importance for understanding its complex spatiotemporal dynamics and cellular functions. Considerable effort has been devoted to the development of small-molecule fluorescent probes for RNA imaging. However, most of the reported studies have mainly focused on improving the photostability, permeability, long emission wavelength, and compatibility with live-cell imaging of RNA probes. Less attention has been paid to the selectivity and detection limit of this class of probes. Highly selective and sensitive RNA probes are still rarely available. In this study, a new set of styryl probes were designed and synthesized, with the aim of upgrading the detection limit and maintaining the selectivity of a lead probe QUID-1 for RNA. Among these newly synthesized compounds, QUID-2 was the most promising candidate. The limit of detection (LOD) value of QUID-2 for the RNA was up to 1.8 ng/mL in solution. This property was significantly improved in comparison with that of QUID-1. Further spectroscopy and cell imaging studies demonstrated the advantages of QUID-2 over a commercially available RNA staining probe, SYTO RNASelect, for highly selective and sensitive RNA imaging. In addition, QUID-2 exhibited excellent photostability and low cytotoxicity. Using QUID-2, the global dynamics of RNA were revealed in live cells. More importantly, QUID-2 was found to be potentially applicable for detecting RNA granules in live cells. Collectively, our work provides an ideal probe for RNA imaging. We anticipate that this powerful tool may create new opportunities to investigate the underlying roles of RNA and RNA granules in live cells.

Development of a Sodium Alginate-Based Active Package with Controlled Release of Cinnamaldehyde Loaded on Halloysite Nanotubes.

The worsening environment and the demand for safer food have accelerated the development of new food packaging materials. The objective of this research is to prepare antimicrobial food packaging film with controlled release by loading cinnamaldehyde (CIN) on etched halloysite nanotubes (T-HNTs) and adding it to sodium alginate (SA) matrix. The effects of T-HNTs-CIN on the physical functional properties and antibacterial activity of the film were systematically evaluated, and the release of CIN in the film was also quantified. Transmission electron microscopy and nitrogen adsorption experiments showed that the halloysite nanotubes had been etched and CIN was successfully loaded into the T-HNTs. The addition of T-HNTs-CIN significantly improved the water vapor barrier properties and tensile strength of the film. Similarly, the presence of T-HNTs-CIN in the film greatly reduced the negative effects of ultraviolet rays. The release experiment showed that the diffusion time of CIN in SA/T-HNTs-CIN film to fatty food simulation solution was delayed 144 h compared with that of SA/CIN film. Herein, the antibacterial experiment also confirmed the controlled release effect of T-HNTs on CIN. In conclusion, SA/T-HNTs-CIN film might have broad application prospects in fatty food packaging.

A pH indicator film based on chitosan and butterfly pudding extract for monitoring fish freshness.

A pH indicator film was prepared by mixing natural polymeric chitosan (CH) with natural dye from butterfly pudding extract (BP). The films were determined by color changes at different pH value, absorbance, thickness, moisture content, swelling property, water contact angle, mechanical property, barrier property, and microstructure of films. The structural change of film was analyzed by Fourier transform infrared spectra. The application to monitor fish freshness was also studied. The prepared film was sensitive to the changes in pH value and showed distinct color changes from pink purple to yellow, with pH value ranging from 1 to 14. The films showed visible color changes from purple-blue to dark green during fish preservation. The total volatile basic nitrogen (TVB-N) content and pH value changes of tilapia were closely related to the visual color changes in film. The result indicated that the fabricated film was a highly pH-sensitive film for monitoring fish freshness.