Lysosome-targeted ruthenium(II) complex encapsulated with pluronic® F-127 induces oncosis in A549 cells.

Transition metal complexes with characteristics of unique packaging in nanoparticles and remarkable cancer cell cytotoxicity have emerged as potential alternatives to platinum-based antitumor drugs. Here we report the synthesis, characterization, and antitumor activities of three new Ruthenium complexes that introduce 5-fluorouracil-derived ligands. Notably, encapsulation of one such metal complex, Ru3, within pluronic® F-127 micelles (Ru3-M) significantly enhanced Ru3 cytotoxicity toward A549 cells by a factor of four. To determine the mechanisms underlying Ru3-M cytotoxicity, additional in vitro experiments were conducted that revealed A549 cell treatment with lysosome-targeting Ru3-M triggered oxidative stress, induced mitochondrial membrane potential depolarization, and drastically reduced intracellular ATP levels. Taken together, these results demonstrated that Ru3-M killed cells mainly via a non-apoptotic pathway known as oncosis, as evidenced by observed Ru3-M-induced cellular morphological changes including cytosolic flushing, cell swelling, and cytoplasmic vacuolation. In turn, these changes together caused cytoskeletal collapse and activation of porimin and calpain1 proteins with known oncotic functions that distinguished this oncotic process from other cell death processes. In summary, Ru3-M is a potential anticancer agent that kills A549 cells via a novel mechanism involving Ru(II) complex triggering of cell death via oncosis.

Cyclometalated iridium(III) complexes induce immunogenic cell death in HepG2 cells via paraptosis.

Immunotherapy has been shown to provide superior antitumor efficacy by activating the innate immune system to recognize, attack and eliminate tumor cells without seriously harming normal cells. Herein, we designed and synthesized three new cyclometalated iridium(III) complexes (Ir1, Ir2, Ir3) then evaluated their antitumor activity. When co-incubated with HepG2 cells, the complex Ir1 localized in the lysosome, where it induced paraptosis and endoplasmic reticulum stress (ER stress). Notably, Ir1 also induced immunogenic cell death (ICD), promoted dendritic cell maturation that enhanced effector T cell chemotaxis to tumor tissues, down-regulated proportions of immunosuppressive regulatory T cells within tumor tissues and triggered activation of antitumor immunity throughout the body. To date, Ir1 is the first reported iridium(III) complex-based paraptosis inducer to successfully induce tumor cell ICD. Furthermore, Ir1 induced ICD of HepG2 cells without affecting cell cycle or reactive oxygen species levels.

Rosin modified aminated mesoporous silica adsorbed tea tree oil sustained-release system for improve synergistic antibacterial and long-term antibacterial effects.

Tea tree oil, a natural antibacterial compound, cannot be used effectively because of its volatile nature. In this work, a biocompatible carrier was prepared and loaded with tea tree essential oil. The carrier was prepared via the electrostatic or chemical action of aminated mesoporous silica and sodium rosin for achieving a low volatilization rate of tea tree essential oil. A synergistic antibacterial effect was observed between sodium rosin and tea tree essential oil. This method utilized the positive charge of the amino group and the condensation reaction with the carboxyl group to achieve physical and chemical interactions with sodium rosin. Fourier Transform Infrared, Brunauer-Emmet-Teller, Zeta potential, SEM, TEM, and TG were performed to characterize the structure and properties of the samples. Compared to the electrostatic effect, the chemically modified system exhibited a longer sustained release, and the sustained release curve followed the Korsmeyer-Peppas release model. Also, the antibacterial properties of the chemically modified system exhibited better minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) respectively, the MIC and MBC forE. coliwere 0.3 mg ml-1and 0.6 mg ml-1respectively, forS. aureuswere 0.15 mg ml-1and 0.3 mg ml-1respectively. More strikingly, the sample also demonstrated long-term antibacterial performance. Therefore, this work provides a new way for the delivery of volatile antibacterial drugs to achieve sustained-release and long-lasting antibacterial effects.

Syntheses, Structures, and Characteristics of Three Metal Complexes Constructed Using Hexacarboxylic Acid.

In this study, three new 3D coordination polymers (CPs), {[Cd3(L)(H2O)6]·H2O}n (1), {[Cu1.5(L)0.5(bimb)1.5]·5H2O·DMF}n (2), and {[Mn1.5(H3L)(bibp)0.5(H2O)2]·3H2O}n (3) (bimb= 1,3-bis(imidazol-1-yl)benzene, bibp= 1,4-bis((4-imidazol-1-yl)benzyl)piperazine), were prepared under solvothermal or hydrothermal conditions based on a hexadentate ligand (1,3,5-triazine-2,4,6-triamine hexa-acetic acid (H6L)). Structural elucidations were carried out by IR spectra along with single-crystal X-ray diffraction analysis, while thermogravimetric analysis (TGA) (dynamic and isothermal) and XRD techniques were used for property evaluations of the polymers. Furthermore, the fluorescence properties and detection of the Fe3+ ions in 1 were tested at room temperature, and the electrochemical behavior of 2 is also stated in this article.

Overexpressing of OsAMT1-3, a High Affinity Ammonium Transporter Gene, Modifies Rice Growth and Carbon-Nitrogen Metabolic Status.

AMT1-3 encodes the high affinity NH4⁺ transporter in rice roots and is predominantly expressed under nitrogen starvation. In order to evaluate the effect of AMT1-3 gene on rice growth, nitrogen absorption and metabolism, we generated AMT1-3-overexpressing plants and analyzed the growth phenotype, yield, carbon and nitrogen metabolic status, and gene expression profiles. Although AMT1-3 mRNA accumulated in transgenic plants, these plants displayed significant decreases in growth when compared to the wild-type plants. The nitrogen uptake assay using a 15N tracer revealed poor nitrogen uptake ability in AMT1-3-overexpressing plants. We found significant decreases in AMT1-3-overexpressing plant leaf carbon and nitrogen content accompanied with a higher leaf C/N ratio. Significant changes in soluble proteins and carbohydrates were also observed in AMT1-3-overexpressing plants. In addition, metabolite profile analysis demonstrated significant changes in individual sugars, organic acids and free amino acids. Gene expression analysis revealed distinct expression patterns of genes that participate in carbon and nitrogen metabolism. Additionally, the correlation between the metabolites and gene expression patterns was consistent in AMT1-3-overexpressing plants under both low and high nitrogen growth conditions. Therefore, we hypothesized that the carbon and nitrogen metabolic imbalance caused by AMT1-3 overexpressing attributed to the poor growth and yield of transgenic plants.

Mitochondria- and endoplasmic reticulum-localizing iridium(III) complexes induce immunogenic cell death of 143B cells.

Recent breakthroughs in cancer immunology have propelled immunotherapy to the forefront of cancer research as a promising treatment approach that harnesses the body's immune system to effectively identify and eliminate cancer cells. In this study, three novel cyclometalated Ir(III) complexes, Ir1, Ir2, and Ir3, were designed, synthesized, and assessed in vitro for cytotoxic activity against several tumor-derived cell lines. Among these, Ir1 exhibited the highest cytotoxic activity, with an IC50 value of 0.4 ± 0.1 µM showcasing its significant anticancer potential. Detailed mechanistic analysis revealed that co-incubation of Ir1 with 143B cells led to Ir1 accumulation within mitochondria and the endoplasmic reticulum (ER). Furthermore, Ir1 induced G0/G1 phase cell cycle arrest, while also diminishing mitochondrial membrane potential, disrupting mitochondrial function, and triggering ER stress. Intriguingly, in mice the Ir1-induced ER stress response disrupted calcium homeostasis to thereby trigger immunogenic cell death (ICD), which subsequently activated the host antitumor immune response while concurrently dampening the in vivo tumor-induced inflammatory response.

Design and implementation of load intensity monitoring platform supported by big data technology in stage training for women's sitting volleyball.

This study aims to discuss the load intensity monitoring in the training process of sitting volleyball, to help coaches understand the training status of athletes, and to provide a scientific basis for the follow-up training plan. Through big data technology, the physiological changes of athletes can be more accurately grasped. This includes classification and summary of exercise load intensity and experimental study of the relationship between heart rate and rating perceived exertion (RPE). Through monitoring the training process of a provincial women's sitting volleyball team, it is found that there is a significant positive correlation between athletes' RPE and average heart rate. This result shows that by monitoring the change in heart rate and RPE of athletes, athletes' training state and physical condition can be more accurately understood. The results reveal that through the use of big data technology and monitoring experiments, it is found that heart rate and RPE are effective monitoring indicators, which can scientifically reflect the load intensity during sitting volleyball training. The conclusions provide coaches with a more scientific basis for making training plans and useful references for sports involving people with disabilities.

8-Hydroxyquinoline ruthenium(II) complexes induce ferroptosis in HeLa cells by down-regulating GPX4 and ferritin.

Ruthenium complexes are one of the most promising anticancer drugs triggered extensive research. Here, the synthesis and characterization of two ruthenium(II) polypyridine complexes containing 8-hydroxylquinoline as ligand, [Ru(dip)2(8HQ)]PF6 (Ru1), [Ru(dpq)2(8HQ)]PF6 (Ru2) (8HQ = 8-hydroxylquinoline; dip = 4,7-diphenyl-1,10-phenanthroline; dpq = pyrazino[2,3-f][1,10]phenanthroline) were reported. On the basis of cytotoxicity tests, Ru1 (IC50 = 1.98 ± 0.02 µM) and Ru2 (IC50 = 10.02 ± 0.19 µM) both showed good anticancer activity in a panel of cell lines, especially in HeLa cells. Researches on mechanism indicated that Ru1 and Ru2 acted on mitochondria and nuclei and induced reactive oxygen species (ROS) accumulation, while the morphology of nuclei and cell cycle had no significant change. Western blot assay further proved that GPX4 and Ferritin were down-regulated, which eventually triggered ferroptosis in HeLa cells. In addition, the toxicity test of zebrafish embryos showed that the concentrations of Ru1 and Ru2 below 120 µM and 60 µM were safe and did not have obvious effect on the normal development of zebrafish embryos.

Engineering the synthesized colloidal CuInS2 passivation layer in interface modification for CdS/CdSe quantum dot solar cells.

Interface modification is an important means to enhance the photovoltaic performance of quantum dot sensitized solar cells (QDSCs). The TiO2/CdS/CdSe solar cells are sensitized with CdS QDs and CdSe QDs, which inevitably introduces a new interface to form a recombination center. Therefore, it is necessary to coat a passivation layer in order to effectively inhibit charge recombination at the CdS/CdSe interface. In this work, CuInS2 (CIS) has been introduced into the CdS/CdSe QD system as an inner passivation layer and the CdS/CIS/CdSe photoanode structure has been fabricated in an environmentally friendly manner. The extracted charge amount (Q) is used to express the charge separation efficiency, indicating that we have obtained outstanding charge extraction efficiency in CIS based CdS/CdSe QDSCs. As a result, the photocurrent density of the TiO2/CdS/CIS/CdSe photoanode significantly has increased from 19.01 mA cm-2 to 22.74 mA cm-2 (TiO2/CdS/CdSe photoanode), which demonstrates a higher photoconversion efficiency of 4.52% in comparison with that of TiO2/CdS/CdSe photoanode.

The potency of lncRNA MALAT1/miR-155/CTLA4 axis in altering Th1/Th2 balance of asthma.

OBJECTIVES: The present study examined if the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/miR-155/CTLA-4 axis was involved in modifying Th1/Th2 balance, a critical indicator for asthma progression. METHODS: Altogether 772 asthma patients and 441 healthy controls were recruited, and their blood samples were collected to determine expressional levels of MALAT1, miR-155, CTLA-4, T-bet, GATA3, Th1-type cytokines and Th2-type cytokines. The CD4+ T cells were administered with pcDNA3.1-MALAT1, si-MALAT1, miR-155 mimic and miR-155 inhibitor to assess their effects on cytokine release. The luciferase reporter gene assay was also adopted to evaluate the sponging relationships between MALAT1 and miR-155, as well as between miR-155 and CTLA-4. RESULTS: Over-expressed MALAT1 and under-expressed miR-155 were more frequently detected among asthma patients who showed traits of reduced forced expiratory failure volume in 1 s (FEV1), FEV1/forced vital capacity (FVC) and FEV1% of predicted (P<0.05). Moreover, MALAT1 expression was negatively expressed with the Th1/Th2 and T-bet/GATA3 ratios, yet miR-155 expression displayed a positively correlation with the ratios (P<0.05). Additionally, the IFN-γ, IL-2 and T-bet levels were reduced under the influence of pcDNA3.1-MALAT1 and miR-155 inhibitor, while levels of IL-4, IL-10 and GATA3 were raised under identical settings (P<0.05). Furthermore, MALAT1 constrained expression of miR-155 within CD4+ T cells by sponging it, and CTLA-4 could interfere with the effects of MALAT1 and miR-155 on Th1/Th2 balance and T-bet/Gata3 ratio (P<0.05). CONCLUSION: MALAT1 sponging miR-155 was involved with regulation of Th1/Th2 balance within CD4+ T cells, which might aid to develop therapies for amelioration of asthmatic inflammation.

A Natural Light/Dark Cycle Regulation of Carbon-Nitrogen Metabolism and Gene Expression in Rice Shoots.

Light and temperature are two particularly important environmental cues for plant survival. Carbon and nitrogen are two essential macronutrients required for plant growth and development, and cellular carbon and nitrogen metabolism must be tightly coordinated. In order to understand how the natural light/dark cycle regulates carbon and nitrogen metabolism in rice plants, we analyzed the photosynthesis, key carbon-nitrogen metabolites, and enzyme activities, and differentially expressed genes and miRNAs involved in the carbon and nitrogen metabolic pathway in rice shoots at the following times: 2:00, 6:00, 10:00, 14:00, 18:00, and 22:00. Our results indicated that more CO2 was fixed into carbohydrates by a high net photosynthetic rate, respiratory rate, and stomatal conductance in the daytime. Although high levels of the nitrate reductase activity, free ammonium and carbohydrates were exhibited in the daytime, the protein synthesis was not significantly facilitated by the light and temperature. In mRNA sequencing, the carbon and nitrogen metabolism-related differentially expressed genes were obtained, which could be divided into eight groups: photosynthesis, TCA cycle, sugar transport, sugar metabolism, nitrogen transport, nitrogen reduction, amino acid metabolism, and nitrogen regulation. Additionally, a total of 78,306 alternative splicing events have been identified, which primarily belong to alternative 5' donor sites, alternative 3' acceptor sites, intron retention, and exon skipping. In sRNA sequencing, four carbon and nitrogen metabolism-related miRNAs (osa-miR1440b, osa-miR2876-5p, osa-miR1877 and osa-miR5799) were determined to be regulated by natural light/dark cycle. The expression level analysis showed that the four carbon and nitrogen metabolism-related miRNAs negatively regulated their target genes. These results may provide a good strategy to study how natural light/dark cycle regulates carbon and nitrogen metabolism to ensure plant growth and development.