Ferroptosis-Enhanced Cancer Immunity by a Ferrocene-Appended Iridium(III) Diphosphine Complex.

Ferroptosis is a programmed cell death pathway discovered in recent years, and ferroptosis-inducing agents have great potential as new antitumor candidates. Here, we report a IrIII complex (Ir1) containing a ferrocene-modified diphosphine ligand that localizes in lysosomes. Under the acidic environments of lysosomes, Ir1 can effectively catalyze Fenton-like reaction, produce hydroxyl radicals, induce lipid peroxidation, down-regulate glutathione peroxidase 4, and result in ferroptosis. RNA sequencing analysis shows that Ir1 can significantly affect pathways related to ferroptosis and cancer immunity. Accordingly, Ir1 can induce immunogenic cells death and suppress tumor growth in vitro, regulate T cell activity and immune microenvironments in vivo. In conclusion, we show the potential of small molecules with ferroptosis-inducing capabilities for effective cancer immunotherapy.

Cardioprotective effects of timosaponin B-II isolated from Anemarrhena rhizome in a zebrafish model.

Timosaponin B-II (TB-II; (25S)-26-(ß-D-glucopyranosyloxy)-3ß-[(2-O-ß-D-glucopyranosyl-ß-D-galactopyranosyl) oxy]-5ß-furostan-22-ol is extracted from Anemarrhena. Its anti-inflammation, anti-oxidation, and anti-asthma properties have been widely explored. However, its effect on the heart has not been reported. In this study, we used zebrafish as a research model to determine the effects of TB-II on the heart and its toxic and anti-inflammatory effects. To explore the cause of cardioprotective effects of TB-II, we used transgenic zebrafish with macrophages and neutrophils labeled with fluorescent protein. We found for the first time that TB-II had a protective effect on the zebrafish heart. It did not affect the survival and hatching rates of zebrafish embryos, indicating its low toxicity. Results showed that TB-II may have cardioprotective effects, which might be related to its anti-inflammatory effects.

Metabolomic profiling of rat urine after oral administration of the prescription antipyretic Hao Jia Xu Re Qing Granules by UPLC/Q-TOF-MS.

Hao Jia Xu Re Qing Granules (HJ), is an effective clinically used antipyretic based on traditional Chinese medicine. Although its antipyretic therapeutic effectiveness is obvious, its therapeutic mechanism has not been comprehensively explored yet. In this research, we first identified potential biomarkers which may be relevant for the antipyretic effect of HJ based on urine metabolomics using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). A rat model of fever was established using the yeast-induced febrile response. Total-ion-current metabolic profiles of different groups were acquired and the data were processed by multivariate statistical analysis-partial least-squares discriminant analysis. As envisioned, the results revealed changes of urine metabolites related to the antipyretic effect. Fourteen potential biomarkers were selected from the urine samples based on the results of Student's t-test, "shrinkage t", variable importance in projection and partial least-squares discriminant analysis. N-Acetylleucine, kynurenic acid, indole-3-ethanol, nicotinuric acid, pantothenic acid and tryptophan were the most significant biomarkers found in the urine samples, and may be crucially related to the antipyretic effect of HJ. Consequently, we propose the hypothesis that the significant antipyretic effect the HJ may be related to the inhibition of tryptophan metabolism. This research thus provides strong theoretical support and further direction to explain the antipyretic mechanism of HJ, laying the foundation for future studies.

[Rapid identification and preliminary study of fragmentation regularity of saponins components of ginseng].

OBJECTIVE: To study a method for rapidly identifying the saponions components in Ginseng and explore the fragmentation regularity. METHODS: Used ACQUITY UPLC/Q-TOF micro system gradient elute wirh 10 mmol/L ammonium acetate-acetonitrile mobile phase under the ESI negative mode; Data were analyzed by Masslynx 4.1 software. RESULTS: 30 kinds of saponins in Ginseng were analyzed and identified by UPLC/Q-TOF-MS, and the fragmentation regularity of ginseng saponins components were explored. CONCLUSION: A analysis method is established for rapid identification of saponin components.

[Spatiotemporal Evolution Characteristics of PM2.5-O3 Compound Pollution in Chinese Cities from 2015 to 2020].

Based on the monitoring data of PM2.5 and O3 concentrations in 333 cities in China from 2015 to 2020, using spatial clustering, trend analysis, and the geographical gravity model, this study quantitatively analyzed the characteristics of PM2.5-O3 compound pollution concentrations and its spatiotemporal dynamic evolution pattern in major cities in China. The results showed that:① there was a synergistic change in PM2.5 and O3 concentrations. When ρ(PM2.5_mean) ≤ 85 µg·m-3, for every 10 µg·m-3 increase in ρ(PM2.5_mean), the peak of the mean value of ρ(O3_perc90) increased by 9.98 µg·m-3. When ρ(PM2.5_mean) exceeded the national Grade II standards of (35±10) µg·m-3, the peak of the mean value of ρ(O3_perc90) increased the fastest, with an average growth rate of 11.81%. In the past six years, on average, 74.97% of Chinese cities with compound pollution had a ρ(PM2.5_mean) in the range of 45 to 85 µg·m-3. When ρ(PM2.5_mean)>85 µg·m-3, the mean value of ρ(O3_perc90) showed a significant decreased trend. ② The spatial clustering pattern of PM2.5 and O3 concentrations in Chinese cities was similar, and hot spots of the six-year mean values of ρ(PM2.5_mean) and ρ(O3_perc90) were distributed in the Beijing-Tianjin-Hebei urban agglomeration and other cities in the Shanxi, Henan, and Anhui provinces. ③ The number of cities with PM2.5-O3 compound pollution showed an interannual variation trend of increasing first (2015-2018) and then decreasing (2018-2020) and a seasonal trend of gradually decreasing from spring to winter. Further, the compound pollution phenomenon mainly occurred in the warm season (April to October). ④ The spatial distribution of PM2.5-O3 compound polluted cities was changing from dispersion to aggregation. From 2015 to 2017, the compound polluted areas spread from the eastern coastal areas to the central and western regions of China, and by 2017, a large-scale polluted area centered on the Beijing-Tianjin-Hebei urban agglomeration, the Central Plains urban agglomeration, and surrounding areas was formed. ⑤ The migration directions of PM2.5 and O3 concentration centers were similar, and there were obvious trends of moving westward and northward. The problem of high-concentration compound pollution was concentrated and highlighted in cities in central and northern China. In addition, since 2017, the distance between the centers of gravity of PM2.5 and O3 concentrations in the compound polluted areas had been significantly reduced, with a reduction of nearly 50%.

Research and application of tongue and face diagnosis based on deep learning.

Objective: To explore the technical research and application characteristics of deep learning in tongue-facial diagnosis. Methods: Through summarizing the merits and demerits of current image processing techniques used in the traditional medical tongue and face diagnosis, the research status of deep learning in tongue image preprocessing, segmentation, and classification was analyzed and reviewed, and the algorithm was compared and verified with the real tongue and face image. Images of the face and tongue used for diagnosis in conventional medicine were systematically reviewed, from acquisition and pre-processing to segmentation, classification, algorithm comparison, result from analysis, and application. Results: Deep learning improved the speed and accuracy of tongue and face diagnostic image data processing. Among them, the average intersection ratio of U-net and Seg-net models exceeded 0.98, and the segmentation speed ranged from 54 to 58 ms. Conclusion: There is no unified standard for lingual-facial diagnosis objectification in terms of image acquisition conditions and image processing methods, thus further research is indispensable. It is feasible to use the images acquired by mobile in the field of medical image analysis by reducing the influence of environmental and other factors on the quality of lingual-facial diagnosis images and improving the efficiency of image processing.

Quantitative tracking of endoplasmic reticulum viscosity during ferroptosis by an iridium complex via TPPLM.

Herein, we report a neutral iridium complex, [Ir(4-(2-pyridinyl)benzaldehyde)2(acetylacetone)] (Ir-ER), with viscosity-responsive phosphorescent emission intensity and lifetime. Quantitative measurement by two-photon phosphorescent lifetime imaging shows that the viscosity of ER increases significantly in the process of erastin-induced ferroptosis. Our work provides an effective strategy for quantitative measurement of the micro-environmental alternations of subcellular organelles during a specific cell death process.

Phosphorescent metal complexes as theranostic anticancer agents: combining imaging and therapy in a single molecule.

Phosphorescent metal complexes are a new kind of multifunctional antitumor compounds that can integrate imaging and antitumor functions in a single molecule. In this minireview, we summarize the recent research progress in this field, concentrating on the theranostic applications of phosphorescent iridium(iii), ruthenium(ii) and rhenium(i) complexes. The molecular design that affords these complexes with tumour- or subcellular organelle-targeting properties is elucidated. The potential of these complexes to induce and monitor the dynamic behavior of subcellular organelles and the changes in microenvironment during the process of therapy is demonstrated. Moreover, the potential and advantages of applying new technologies, such as super-resolution imaging and phosphorescence lifetime imaging, are also described. Finally, the challenges faced in the development of novel theranostic metallo-anticancer complexes for possible clinical translation are proposed.

Shedding lights on the flexible-armed porphyrins: Human telomeric G4 DNA interaction and cell photocytotoxicity research.

DNA polymorphism exerts a fascination on a large scientific community. Without crystallographic structural data, clarification of the binding modes between G-quadruplex (G4) and ligand (complex) is a challenging job. In the present work, three porphyrin compounds with different flexible carbon chains (arms) were designed, synthesized and characterized. Their binding, folding and stabilizing abilities to human telomeric G4 DNA structures were comparatively researched. Positive charges at the end of the flexible carbon chains seem to be favorable for the DNA-porphyrin interactions, which were evidenced by the spectral results and further confirmed by the molecular docking calculations. Biological function analysis demonstrated that these porphyrins show no substantial inhibition to Hela, A549 and BEL 7402 cancer cell lines under dark while exhibit broad inhibition under visible light. This significantly enhanced photocytotoxicity relative to the dark control is an essential property of photochemotherapeutic agents. The feature of the flexible arms emerges as critical influencing factors in the cell photocytotoxicity. Moreover, an ROS-mediated mitochondrial dysfunction pathway was suggested for the cell apoptosis induced by these flexible-armed porphyrins. It is found that the porphyrins with positive charges located at the end of the flexible arms represent an exciting opportunity for photochemotherapeutic anti-cancer drug design.