Contrast agents (CAs) play a crucial role in high-quality magnetic resonance imaging (MRI) applications. At present, as a result of the Gd-based CAs which are associated with renal fibrosis as well as the inherent dark imaging characteristics of superparamagnetic iron oxide nanoparticles, Mn-based CAs which have a good biocompatibility and bright images are considered ideal for MRI. In addition, manganese oxide nanoparticles (MONs, such as MnO, MnO₂, Mn₃O₄, and MnO_x) have attracted attention as T1-weighted magnetic resonance CAs due to the short circulation time of Mn(II) ion chelate and the size-controlled circulation time of colloidal nanoparticles. In this review, recent advances in the use of MONs as MRI contrast agents for tumor detection and diagnosis are reported, as are the advances in in vivo toxicity, distribution and tumor microenvironment-responsive enhanced tumor chemotherapy and radiotherapy as well as photothermal and photodynamic therapies.

Background: Postoperative chemotherapy for gastric cancer often causes multidrug resistance (MDR), which has serious consequences for therapeutic effects. Individualized treatment based on accurate monitoring of MDR will greatly improve patient survival. Results: In this article, a self-enhanced Mn₃O₄ nanoplatform (MPG NPs) was established, which can react with glutathione to produce Mn²⁺ to enhance T1-weighted magnetic resonance imaging (MRI) and mediate in vivo real-time MDR monitoring. In vitro MRI results showed that MRI signals could be enhanced in the presence of hydrogen peroxide and glutathione and at acidic pH. In vivo MRI results indicated that MPG NPs could specifically target MDR cells, thereby realizing real-time monitoring of MDR in gastric cancer. Furthermore, MPG NPs have good chemodynamic activity, which can convert the endogenous hydrogen peroxide of tumor cells into highly toxic hydroxyl radical through Fenton-like reaction at acidic pH to play the role of chemodynamic therapy. In addition, Mn₃O₄ can significantly enhance the chemodynamic therapy effect because of its good photothermal conversion effect. Furthermore, in situ photothermal/chemodynamic synergistic therapy obtained remarkable results, the tumors of the mice in the synergistic therapy group gradually became smaller or even disappeared. Conclusions: MPG NPs have good biocompatibility, providing a good nanoplatform for real-time monitoring and precise diagnosis and treatment of MDR in gastric cancer. Graphical

Auxin response factor (ARF) is a transcription factor that can specifically bind to the promoter of auxin-responsive genes in plants and plays an important regulatory role in plant growth and development. The previous studies have predicted 25 ARF genes in Sorghum bicolor (SbARFs) and indicated that SbARFs play complex roles in salt and drought stresses. In this study, we reclassified and analyzed the structures of ARFs in three plants, including sorghum, rice, and Arabidopsis. Phylogenetic analyses categorized 73 ARF into five classes. By studying the characterization of the structures, it was found that SbARFs from the same evolutionary branches showed similar motif patterns. Furthermore, the expression patterns of SbARF genes during development and temperature stress were investigated in sorghum. Quantitative transcription-quantitative polymerase chain reaction (qRT-PCR) results suggested that they had different expression patterns in vegetative and reproductive organs at various developmental stages. High and low-temperature treatments and qRT-PCR demonstrated some of them changed dramatically along with the increase of treatment time. Additionally, in situ hybridization results displayed that SbARF genes were accumulated in vascular tissues under temperature stress. These findings provide evidence that SbARFs may play important roles in sorghum vegetative development, reproductive development, and auxin response to temperature stress.

Multifunctional manganese oxide nanoparticles (NPs) with impressive enhanced T₁ contrast ability show great promise in biomedical diagnosis. Herein, we developed a dual-modality imaging agent system based on polyethylene glycol (PEG)-coated manganese oxide NPs conjugated with organic dye (Cy_7.5), which functions as a fluorescence imaging (FI) agent as well as a magnetic resonance imaging (MRI) imaging agent. The formed Mn₃O₄@PEG-Cy_7.5 NPs with the size of ~10 nm exhibit good colloidal stability in different physiological media. Serial FI and MRI studies that non-invasively assessed the bio-distribution pattern and the feasibility for in vivo dual-modality imaging-guided lymph node mapping have been investigated. In addition, histological and biochemical analyses exhibited low toxicity even at a dose of 20 mg/kg in vivo. Since Mn₃O₄@PEG-Cy_7.5 NPs exhibited desirable properties as imaging agents and good biocompatibility, this work offers a robust, safe, and accurate diagnostic platform based on manganese oxide NPs for tumor metastasis diagnosis.

Background: Hypoxia-activated prodrugs present new opportunities for safe and effective tumor drug resistance therapy due to their high selectivity for hypoxic cells. However, the uneven distribution of oxygen in solid tumor and insufficient hypoxia in the tumor microenvironment greatly limit its therapeutic efficacy. Results: In this paper, a novel AQ4N-Mn(II)@PDA coordination nanoplatform was designed and functionalized with GMBP1 to target drug-resistant tumor cells. Its excellent photothermal conversion efficiency could achieve local high-temperature photothermal therapy in tumors, which could not only effectively exacerbate tumor hypoxia and thus improve the efficacy of hypoxia-activated chemotherapy of AQ4N but also significantly accelerate Mn²⁺-mediated Fenton-like activity to enhance chemodynamic therapy. Moreover, real-time monitoring of blood oxygen saturation through photoacoustic imaging could reflect the hypoxic status of tumors during treatment. Furthermore, synergistic treatment effectively inhibited tumor growth and improved the survival rate of mice bearing orthotopic drug-resistant tumors. Conclusions: This study not only provided a new idea for PTT combined with hypoxia-activated chemotherapy and CDT for drug-resistant tumors but also explored a vital theory for real-time monitoring of hypoxia during treatment.