Promoting reactive oxygen species accumulation to overcome tyrosine kinase inhibitor resistance in cancer.

BACKGROUND: In tumor treatment, protein tyrosine kinase inhibitors (TKIs) have been extensively utilized. However, the efficacy of TKI is significantly compromised by drug resistance. Consequently, finding an effective solution to overcome TKI resistance becomes crucial. Reactive oxygen species (ROS) are a group of highly active molecules that play important roles in targeted cancer therapy including TKI targeted therapy. In this review, we concentrate on the ROS-associated mechanisms of TKI lethality in tumors and strategies for regulating ROS to reverse TKI resistance in cancer. MAIN BODY: Elevated ROS levels often manifest during TKI therapy in cancers, potentially causing organelle damage and cell death, which are critical to the success of TKIs in eradicating cancer cells. However, it is noteworthy that cancer cells might initiate resistance pathways to shield themselves from ROS-induced damage, leading to TKI resistance. Addressing this challenge involves blocking these resistance pathways, for instance, the NRF2-KEAP1 axis and protective autophagy, to promote ROS accumulation in cells, thereby resensitizing drug-resistant cancer cells to TKIs. Additional effective approaches inducing ROS generation within drug-resistant cells and providing exogenous ROS stimulation. CONCLUSION: ROS play pivotal roles in the eradication of tumor cells by TKI. Harnessing the accumulation of ROS to overcome TKI resistance is an effective and widely applicable approach.

Eu3+-functionalized covalent organic framework for ratiometric fluorescence detection and adsorption of tetracycline and information steganography.

Functional materials with organic/inorganic composites as the main matrix and rare earth ion complexes as the guest have shown a very broad application prospect for antibiotic sensors. However, Eu3+-complex often relies on a single fluorescence response signal, which is susceptible to changes in the detection environment and cannot simultaneously detect and remove tetracycline (TC). Herein, green fluorescent covalent two-dimensional organic framework (COF-TD) is synthesized, followed by modification of Eu3+ to synthesize COF-TD@Eu3+. In the ratiometric sensor, Eu3+ serves as the recognition site and specific response probe for TC, while COF-TD is the fluorescence reference and carrier for Eu3+. Due to the antenna effect, TC enhances the red fluorescence of Eu3+, while the green fluorescence of COF-TD remains almost stable. Based on the change of fluorescence intensity and fluorescence color from green to red, the efficient ratiometric sensing can be finished in 1 min. The developed method shows high sensitivity with a detection limit of 0.3 µM and high selectivity to TC which makes the method applicable to detect TC in traditional Chinese medicine preparations. In addition, due to the high specific surface area of COFs and specific adsorption sites, COF-TD@Eu3+ also shows good performance for TC removal. The findings show that the maximum adsorption capacity is 137.3 mg g-1 and the adsorption equilibrium is reached in 30 min. Smartphone assisted COF-TD@Eu3+ for both ratiometric fluorescence detection and detecting the absorption of TC is proposed for the first time. The molecular cryptosteganography that transforms the selective response of COF-TD@Eu3+ to binary strings is anticipated to advance utilization of nanomaterials in logic sensing and information safety.

Concurrent manipulation of competitive mechanisms to construct glutathione-stabilized gold nanocluster-based dual-channel molecular classifier for metal ions detection and information steganography.

Understanding charge transport in metal ion-mediated glutathione-stabilized gold nanoclusters (GSH-Au NCs) has proved difficult due to the presence of various competitive mechanisms, such as electron transfer (ET) and aggregation induction effect (AIE). In this paper, we present a dual-channel fluorescence (FL) and second-order Rayleigh scattering (SRS) sensing method for high-throughput classification of metal ions, relying on the competition between ET and AIE using GSH-Au NCs. The SRS signals show significant enhancement when Pb2+, Ag+, Al3+, Cu2+, Fe3+, and Hg2+ are present, as a result of the aggregation of GSH-Au NCs. Notably, the fluorescence signal exhibits the opposite trend. The FL intensities of GSH-Au NCs are enhanced by Pb2+, Ag+, and Al3+ through the AIE mechanism, while they are quenched by Cu2+, Fe3+, and Hg2+, which is dominated by the ET mechanism. By employing principal component analysis and hierarchical cluster analysis, these signals are transformed into unique fingerprints and Euclidean distances, respectively, enabling successful distinction of six metal ions and their mixtures with a low detection limit of 30 nM. This new strategy has successfully addressed interference from impurities in the testing of real water samples, demonstrating its strong ability to detect multiple metal ions. Impressively, we have achieved molecular cryptosteganography, which involves encoding, storing, and concealing information by transforming the selective response of GSH-Au NCs to binary strings. This research is anticipated to advance utilization of nanomaterials in logic sensing and information safety, bridging the gap between molecular sensors and information systems.

Comparison of bronchial methylene blue staining and modified inflation-deflation method in identifying the intersegmental plane during lung segmentectomy.

Background: Identification of the intersegmental plane (ISP) is the critical step in lung segmentectomy because of the complicated anatomic variations. Bronchial methylene blue staining was developed by our team in 2015 and is now commonly used at our center, it could rapidly and accurately identify the ISP. In this study, we aimed to compare bronchial methylene blue staining with the modified inflation-deflation method in terms of their perioperative characteristics and to present our experience of the methylene blue method. Methods: From June 2020 to September 2021, the data of 112 patients with pulmonary ground-glass nodules who underwent segmentectomy by video-assisted thoracoscopic surgery were retrospectively reviewed. Sixty-two patients underwent bronchial methylene blue staining, and 50 patients underwent the modified inflation-deflation method. Results: Both methods could accurately identify the ISP. The time taken to clearly display the ISP (82.94±28.08 vs. 868.20±145.89 seconds; P<0.001) and the surgical duration (131.69±32.05 vs. 146.08±28.11 minutes; P=0.014) were significantly shorter in the bronchial methylene blue staining group than in the modified inflation-deflation group. There were no significant differences between the two groups in the bleeding volume, drainage time, and length of postoperative hospital stay, as well as in most other perioperative characteristics. Conclusions: Compared with the modified inflation-deflation method, the bronchial methylene blue staining method can quickly display the ISP and shorten the surgical duration. This method is safe and feasible, can be widely applied during thoracoscopic anatomic segmentectomy.

[Expression of PKB protein in human squamous-cell carcinoma and adenocarcinoma of lung].

OBJECTIVE: To investigate the expression of protein kinase B (PKB) in human-squamous cell carcinoma (SCC) and adenocarcinoma of lung (ADC) and in benign lung tissues (BD, lung tissues adjacent to cancer or from patients with benign lung diseases), and its association to clinicopathological characteristics. METHODS: The PKB expression in 41 specimens from patients with SCC (26 cases) and ADC (15 cases) and in 12 specimens from patients with benign lung diseases (BD) were investigated by immunohistochemistry and Western blot analysis. RESULTS: PKB in benign lung tissues was usually weakly stained and scattered in distribution. It was remarkably increased in lung cancer compared to benign lung tissue. The positive rates of PKB in SCC and ADC were 50% (13/26), 60% (9/15), respectively, and there was no significant difference between them. PKB expression was significantly stronger in lung cancer patients in advanced stages (stage III or IV) or with poor differentiation, than those in early stages (stage I or II) or with moderate or well differentiation. The expression was stronger in patients with local lymph node metastasis than those without (P = 0.0391). CONCLUSION: PKB protein is over-expressed in human squamous-cell carcinoma and adenocarcinoma of lung.