Self-Monitoring Theranostic Nanomaterials: Emerging Visual Agents for Real-Time Monitoring of Tumor Treatment Processes.

Self-monitoring in tumor therapy is a concept that allows for real-time monitoring of the location and state of applied nanomaterials. This monitoring relies on dynamic signals, such as wave or magnetic signals, which vary in response to changes in the location and state of nanomaterials. Dynamic changes in nanomaterials can be monitored using dynamic signals, making it possible to determine and control the treatment process. Theranostic nanomaterials, which possess unique physical and chemical properties, have recently been explored as a viable option for self-monitoring. With the help of self-monitoring, theranostic nanomaterials can guide themselves to achieve region-selective treatment with higher controllability and safety. In this review, self-monitoring theranostic nanomaterials will be introduced in three parts according to their roles during therapy: tumor accumulation, tumor therapy, and metabolism. The limitations and future challenges of current self-monitoring theranostic nanomaterials will also be discussed.

Redox Homeostasis Disruptors Based on Metal-Phenolic Network Nanoparticles for Chemo/Chemodynamic Synergistic Tumor Therapy through Activating Apoptosis and Cuproptosis.

The combination of chemo/chemodynamic therapy is a promising strategy for improving antitumor efficacy. Herein, metal-phenolic network nanoparticles (NPs) self-assembled from copper ions and gallic acid (Cu-GA) are developed to evoke apoptosis and cuproptosis for synergistic chemo/chemodynamic therapy. The Cu-GA NPs are biodegraded in response to the highly expressed glutathione (GSH) in tumor cells, resulting in the simultaneous release of Cu+ and GA. The intracellular GSH content is dramatically reduced by the released GA, rendering the tumor cells incapable of scavenging reactive oxygen species (ROS) and more susceptible to cuproptosis. Meanwhile, ROS levels within the tumor cells are significantly increased by the Fenton-like reaction of released Cu+ , which disrupts redox homeostasis and achieves apoptosis-related chemodynamic therapy. Moreover, massive accumulation of Cu+ in the tumor cells further induces aggregation of lipoylated dihydrolipoamide S-acetyltransferase and downregulation of iron-sulfur cluster protein, activating cuproptosis to enhance the antitumor efficacy of Cu-GA NPs. The experiments in vivo further demonstrate that Cu-GA NPs exhibited the excellent biosafety and superior antitumor capacity, which can efficiently inhibit the growth of tumors due to the activation by the tumor specific GSH and hydrogen peroxide. These Cu-based metal-phenolic network NPs provide a potential strategy to build up efficient and safe cancer therapy.

Rapid and Visual Detection of Heterodera schachtii Using Recombinase Polymerase Amplification Combined with Cas12a-Mediated Technology.

Heterodera schachtii is a well-known cyst nematode that causes serious economic losses in sugar beet production every year. Rapid and visual detection of H. schachtii is essential for more effective prevention and control. In this study, a species-specific recombinase polymerase amplification (RPA) primer was designed from a specific H. schachtii sequence-characterized amplified region (SCAR) marker. A band was obtained in reactions with DNA from H. schachtii, but absent from nontarget cyst nematodes. The RPA results could be observed by the naked eye, using a lateral flow dipstick (LFD). Moreover, we combined CRISPR technology with RPA to identify positive samples by fluorescence detection. Sensitivity analysis indicated that 10-4 single cysts and single females, 4-3 single second-stage juveniles, and a 0.001 ng genomic DNA template could be detected. The sensitivity of the RPA method for H. schachtii detection is not only higher than that of PCR and qPCR, but can also provide results in <1 h. Consequently, the RPA assay is a practical and useful diagnostic tool for early diagnosis of plant tissues infested by H. schachtii. Sugar beet nematodes were successfully detected in seven of 15 field sugar beet root samples using the RPA assay. These results were consistent with those achieved by conventional PCR, indicating 100% accuracy of the RPA assay in field samples. The RPA assay developed in the present study has the potential for use in the direct detection of H. schachtii infestation in the field.

Carbothermal Reduction Synthesis of Aluminum Nitride from Al(OH)3/C/PVB Slurries Prepared by Three-Roll Mixing.

Polyvinyl butyral (PVB) was used in the Al(OH)3/carbon black/ethanol slurries by the three-roll mixing to prepare AlN powder using the carbothermal reduction-nitridation (CRN) process in the experiments. The effects of PVB addition on the synthesis of AlN powder were studied by viscosity, tap density, XRD, SEM and TG measurements. The results showed that the PVB layer covering on the surface of Al(OH)3 particles reduced the viscosity of Al(OH)3/carbon/ethanol slurry and increased the dispersion homogeneity of Al(OH)3/carbon raw powder. The tap densities of the Al(OH)3/carbon mixtures after three-roll milling could be increased with the increase in PVB addition. In the CRN process, most of the PVB covering Al(OH)3 particles evaporated and supplied the passage for nitrogen removal to the particles. Based on the experimental data, the role of PVB on the mixing and CRN process was discussed.

H2O2-independent chemodynamic therapy initiated from magnetic iron carbide nanoparticle-assisted artemisinin synergy.

Chemodynamic therapy (CDT) is a booming technology that utilizes Fenton reagents to kill tumor cells by transforming intracellular H2O2 into reactive oxygen species (ROS), but insufficient endogenous H2O2 makes it difficult to attain satisfactory antitumor results. In this article, a H2O2-free CDT technique with tumor-specificity is developed by using pH-sensitive magnetic iron carbide nanoparticles (PEG/Fe2C@Fe3O4 NPs) to trigger artemisinin (ART) to in situ form ROS. ART-loaded PEG/Fe2C@Fe3O4 NPs are fabricated for the enormous release of Fe2+ ions induced by the acidic conditions of the tumor microenvironment after magnetic-assisted tumor enrichment, which results in the rapid degradation of the PEG/Fe2C@Fe3O4 NPs and release of ART once endocytosed into tumor cells. In situ catalysis reaction between the co-released Fe2+ ions and ART generates toxic ROS and then induces apoptosis of tumor cells. Both in vitro and in vivo experiments demonstrate that the efficient Fe-enhanced and tumor-specific CDT efficacy for effective tumor inhibition based on ROS generation. This work provides a new direction to improve CDT efficacy based on H2O2-independent ROS generation.

Identification and Characterization of a Novel Protein Disulfide Isomerase Gene (MgPDI2) from Meloidogyne graminicola.

Protein disulfide isomerase (PDI) is a multifunctional enzyme that catalyzes rate-limiting reactions such as disulfide bond formation, isomerization, and reduction. There is some evidence that indicates that PDI is also involved in host-pathogen interactions in plants. In this study, we show that the rice root-knot nematode, Meloidogyne graminicola, has evolved a secreted effector, MgPDI2, which is expressed in the subventral esophageal glands and up-regulated during the early parasitic stage of M. graminicola. Purified recombinant MgPDI2 functions as an insulin disulfide reductase and protects plasmid DNA from nicking. As an effector, MgPDI2 contributes to nematode parasitism. Silencing of MgPDI2 by RNA interference in the pre-parasitic second-stage juveniles (J2s) reduced M. graminicola multiplication and also increased M. graminicola mortality under H2O2 stress. In addition, an Agrobacterium-mediated transient expression assay found that MgPDI2 caused noticeable cell death in Nicotiana benthamiana. An intact C-terminal region containing the first catalytic domain (a) with an active motif (Cys-Gly-His-Cys, CGHC) and the two non-active domains (b and b') is required for cell death induction in N. benthamiana. This research may provide a promising target for the development of new strategies to combat M. graminicola infections.

Magnetic Reactive Oxygen Species Nanoreactor for Switchable Magnetic Resonance Imaging Guided Cancer Therapy Based on pH-Sensitive Fe5C2@Fe3O4 Nanoparticles.

Reactive oxygen species (ROS) are crucial molecules in cancer therapy. Unfortunately, the therapeutic efficiency of ROS is unsatisfactory in clinic, primarily due to their rigorous production conditions. By taking advantage of the intrinsic acidity and overproduction of H2O2 in the tumor environment, we have reported an ROS nanoreactor based on core-shell-structured iron carbide (Fe5C2@Fe3O4) nanoparticles (NPs) through the catalysis of the Fenton reaction. These NPs are able to release ferrous ions in acidic environments to disproportionate H2O2 into •OH radicals, which effectively inhibits the proliferation of tumor cells both in vitro and in vivo. The high magnetization of Fe5C2@Fe3O4 NPs is favorable for both magnetic targeting and T2-weighted magnetic resonance imaging (MRI). Ionization of these NPs simultaneously decreases the T2 signal and enhances the T1 signal in MRI, and this T2/T1 switching process provides the visualization of ferrous ions release and ROS generation for the supervision of tumor curing. These Fe5C2@Fe3O4 NPs show great potential in endogenous environment-excited cancer therapy with high efficiency and tumor specificity and can be guided further by MRI.

Meloidogyne graminicola protein disulfide isomerase may be a nematode effector and is involved in protection against oxidative damage.

The rice root-knot nematode, Meloidogyne graminicola, is a serious pest in most rice-growing countries. Usually, nematodes employ antioxidants to counteract the harm of reactive oxygen species (ROS) and facilitate their infection. Here the gene encoding M. graminicola protein disulphide isomerase (MgPDI) was identified. The deduced protein is highly conserved in the putative active-site Cys-Gly-His-Cys. In situ hybridization showed that MgPDI was specifically localized within esophageal glands of pre-parasitic second stage juveniles (J2s). MgPDI was significantly up-regulated in the late parasitic J2s. Characterization of the recombinant protein showed that the purified MgPDI exhibited similar activities to other oxidases/isomerases such as the refolding of the scrambled RNase and insulin disulfide reductase and the protection of plasmid DNA and living cells from ROS damage. In addition, silencing of MgPDI by RNA interference in the pre-parasitic J2s lowered their multiplication factor. MgPDI expression was up-regulated in the presence of exogenous H2O2, whereas MgPDI silencing resulted in an increase in mortality under H2O2 stress. MgPDI is localized in the apoplast when transient expression in Nicotiana benthamiana leaves. The results indicated that MgPDI plays important roles in the reproduction and pathogenicity of M. graminicola and it also contributes to protecting nematodes from exogenous H2O2 stress.

Characterization of the Virulence Phenotypes of Heterodera glycines in Minnesota.

Knowledge of the virulence phenotypes of soybean cyst nematode, Heterodera glycines populations is important in choosing appropriate sources for breeding resistant cultivars and managing the nematode. We investigated races of 59 H. glycines populations collected from 1997 to 1998 and races and HG Types of 94 populations collected in 2002 from soybean fields across southern and central Minnesota. In the 1997 to 1998 samples, race 3 was predominant and represented 78% of the populations. The remaining populations were 11.9% race 1, 1.7% race 4, 6.8% race 6, and 1.7% race 14. In the 2002 samples, the populations were classified as 15.3% race 1, 77.6% race 3, 2.4% race 5, 3.5% race 6 and 1.2% race 9. Percentage of 1997 to 1998 populations with female indices (FI) higher than 10 were 10.2% on Pickett 71, 3.4% on Peking, 13.6% on PI 88788, 3.4% on PI 90763, 1.7% on PI 209332, and 1.7% on PI 437654. Percentage of 2002 populations with FI >10 was 1.1% on Peking, 17.0% on PI88788, 14.9% on PI 209332, 33.0% on PI 548316, 11.7% on Pickett 71, and 0% on the other three indicators, PI 90763, PI 437654, and PI 89772. The line PI 548316 was relatively susceptible to the Minnesota H. glycines populations and may not be recommended for breeding resistant cultivars in the state. There was no noticeable change of frequencies of virulence phenotypes in response to the use of resistant cultivars during 1997 to 2002 in Minnesota except that FI increased on the PI 209332.