Citric Acid and Polyvinyl Alcohol Induced PEDOT: PSS with Enhanced Electrical Conductivity and Stretchability for Eco-Friendly, Self-Healable, Wearable Organic Thermoelectrics.

Poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (PEDOT: PSS) is a promising material for organic thermoelectric (TE) applications. However, it is challenging to achieve PEDOT: PSS composites with stretchable, self-healable, and high TE performance. Furthermore, some existing self-healing TE materials employ toxic reagents, posing risks to human health and the environment. In this study, a novel intrinsically self-healable and wearable composite is developed by incorporating environmentally friendly, highly biocompatible, and biodegradable materials of polyvinyl alcohol (PVA) and citric acid (CA) into PEDOT: PSS. This results in the formation of double hydrogen bonding networks among CA, PVA, and PEDOT: PSS, inducing microstructure alignment and leading to simultaneous enhancements in both TE performance and stretchability. The resulting composites exhibit a high electrical conductivity and power factor of 259.3 ± 11.7 S·cm-1, 6.9 ± 0.4 µW·m-1·K-2, along with a tensile strain up to 68%. Furthermore, the composites display impressive self-healing ability, with 84% recovery in electrical conductivity and an 85% recovery in tensile strain. Additionally, the temperature and strain sensors based on the PEDOT: PSS/PVA/CA are prepared, which exhibit high resolution suitable for human-machine interaction and wearable devices. This work provides a reliable and robust solution for the development of environmentally friendly, self-healing and wearable TE thermoelectrics.

Superhydrophilic polyethersulfone (PES) membranes with high scale inhibition properties obtained through bionic mineralization and RTIPS.

Reverse thermally induced separation (RTIPS) was used to obtain a separation membrane with a better internal structure for a higher water flux and a surface that could easily form a hydration layer. In comparison to the traditional modification method, this work focused on the aspect that the internal structure obtained by changing the membrane-making method provided easier adhesion conditions for the dopamine/TiO2 hybrid nanoparticles (DA/TiO2 HNPs) obtained by biomimetic mineralization. It provided a basis for exploring the variation in adhesion with the water bath temperature and the amount of titanium added through the study of turbidity point, SEM images, water contact angle, thermogravimetric test, EDX, AFM, XPS, FTIR and other test results. The SEM images proved that the membrane obtained through the RTIPS method had a porous surface and spongy internal structure, furthermore, additional polymers were adsorbed. Use of EDX demonstrated that biomimetic mineralization prevented the production of agglomerated titanium dioxide. XPS and FTIR spectra confirmed the introduction and immobilization of HNP aggregation. Moreover, a decrease in the surface roughness and water contact angle further suggested an improvement in the hydrophilicity of the modified membrane. The introduction of HNP at a higher water bath temperature helped increase the water flux up to ten times, moreover, the oil-water separation efficiency could still reach over 99.50%. Lastly, a cycle test of the modified membrane under the optimal conditions helped confirm that the membrane forming conditions at this time could provide a better environment for the formation of the hydrophilic layer, which was conducive to the recycling of the separation membrane. In summary, more fixed more hydrophilic particles could be obtained through the RTIPS method based on biomimetic mineralization to prevent the accumulation of titanium dioxide, thus helping improve permeability and anti-fouling of the membrane.

Salvianolic Acid B Protects Cardiomyocytes from Ischemia/Reperfusion Injury by Mediating circTRRAP/miR-214-3p/SOX6 Axis.

Circular RNAs (circRNAs) are a class of powerful regulators of gene expression. This study aimed to determine whether circTRRAP (hsa_circ_0081241) was implicated in the cardioprotective effects of salvianolic acid B (Sal B) against myocardial ischemia/reperfusion (I/R) injury and its associated mechanism.Cell viability was analyzed using Cell Counting Kit-8 (CCK-8), and flow cytometry was conducted to evaluate cell cycle progression and cell apoptosis. The leakage of lactic dehydrogenase (LDH), production of malondialdehyde (MDA), and activity of superoxide dismutase (SOD) were measured using their corresponding commercial kits to analyze cell death and oxidative stress.I/R treatment suppressed viability and cell cycle progression and induced the apoptosis and oxidative stress of AC16 cardiomyocytes, whereas Sal B protected AC16 cardiomyocytes against I/R injury. I/R upregulated circTRRAP expression, whereas Sal B dose-dependently reduced the circTRRAP level in AC16 cardiomyocytes. The protective effects of Sal B in I/R-induced AC16 cardiomyocytes were overturned by the overexpression of circTRRAP. CircTRRAP negatively regulated miR-214-3p expression by binding to it in AC16 cardiomyocytes. The circTRRAP overexpression-mediated effects were reversed by the addition of miR-214-3p mimics in AC16 cardiomyocytes. MiR-214-3p targeted the 3'-untranslated region (3'UTR) of SOX6, and SOX6 was regulated by the circTRRAP/miR-214-3p axis in AC16 cardiomyocytes. SOX6 knockdown overturned the circTRRAP overexpression-induced effects in AC16 cardiomyocytes.In conclusion, the silence of circTRRAP was implicated in Sal B-mediated cardioprotective effects against I/R injury by regulating the miR-214-3p/SOX6 axis.

Development of hydrophilic PES membranes using F127 and HKUST-1 based on the RTIPS method: Mitigate the permeability-selectivity trade-off.

In this study, to mitigate the permeability-selectivity trade-off effect, Pluronic F127 (F127) and HKUST-1 were employed to construct high-performance membranes based on the reverse thermally induced phase separation (RTIPS) method. F127, as a hydrophilic modifier, was applied to increase permeability and resist polyethersulfone (PES) membrane fouling, while the collapse of HKSUT-1 caused by its instability in pure water improved the permeability and selectivity of the membrane. Characterizations demonstrated the successful synthesis of HKUST-1, together with the successful introduction of HKSUT-1 and F127 in PES membranes. It was observed that the membrane prepared by the RTIPS process possessed a uniformly porous surface and sponge-like cross-section with excellent mechanical properties, higher permeability, and selectivity compared to the dense skin and finger-like cross-section of the membrane prepared by the nonsolvent induced phase separation (NIPS) method. Moreover, the permeation and bovine serum albumin (BSA) rejection rate of the optimal membrane reached 2378 L/m2 h and 89.3%, respectively, which were far higher than those of the pure membrane. Hydrophilic F127 and many microvoids formed by the collapse of HKUST-1, played an important role in excellent antifouling properties, high permeability, and selectivity by pure water flux (PWF), flux recovery rate (FRR), BSA flux, and COD removal rate tests. Overall, the membrane with F127 and HKSUT-1 prepared via the RTIPS method not only obtained excellent antifouling properties but also mitigated the permeability-selectivity trade-off.

The Application of Crisis Intervention in Middle-Aged and Young Patients with Acute Myocardial Infarction after PCI.

OBJECTIVE: To investigate the effect of crisis intervention in middle-aged and young patients with acute myocardial infarction after percutaneous coronary stent implantation (PCI). METHODS: A total of 108 middle-aged and young patients with acute myocardial infarction undergoing PCI were selected from July 2018 to July 2019 in the Department of Cardiology, Hai'an County People's Hospital. They were divided into two groups, according to a random number table, with 54 cases in each group. The control group implemented routine postoperative intervention, and the intervention group implemented postoperative crisis intervention. The changes in the two groups' sense of crisis, mental state, quality of life and hope level before and after the intervention were compared. RESULTS: The emotional, behavioral, and cognitive scores of the intervention group were lower than those of the control group after 4 weeks of intervention (P < .05). The mental state scores of the intervention group were lower than those of the control group (P < .05). Also, the various quality of life scores were higher than those of the control group (P < .05). The intervention group's hope level scores were higher than the control group (P < .05) after 4 weeks of intervention. CONCLUSION: The application of crisis intervention to middle-aged and young patients with acute myocardial infarction after PCI can reduce the sense of crisis, improve their mental state and quality of life, and raise the level of hope.

Polar Side Chain Effects on the Thermoelectric Properties of Benzo[1,2-b:4,5-b']Dithiophene-Based Conjugated Polymers.

The molecular structure of polymers has a great influence on their thermoelectric properties; however, the relationship between the molecular structure of a polymer and its thermoelectric properties remains unclear. In this work, two benzo[1,2-b:4,5-b']dithiophene (BDT)-based conjugated polymers are designed and synthesized, which contain alkyl side chains or polar side chains. The effects of the polymer side chain on the physicochemical properties are systematically investigated, especially the thermoelectric performance of the polymers after doping with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone and 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane. It is found that the BDT-based conjugated polymer with polar side chains exhibits good miscibility with the dopants, leading to higher thermoelectric properties than those of the polymer with alkyl side chains. This work can serve as a reference for the future design of high-performance organic thermoelectric polymers.

Development of a versatile DNMT and HDAC inhibitor C02S modulating multiple cancer hallmarks for breast cancer therapy.

DNMT and HDAC are closely related to each other and involved in various human diseases especially cancer. These two enzymes have been widely recognized as antitumor targets for drug discovery. Besides, research has indicated that combination therapy consisting of DNMT and HDAC inhibitors exhibited therapeutic advantages. We have reported a DNMT and HDAC dual inhibitor 15a of which the DNMT enzymatic inhibitory potency needs to be improved. Herein we reported the development of a novel dual DNMT and HDAC inhibitor C02S which showed potent enzymatic inhibitory activities against DNMT1, DNMT3A, DNMT3B and HDAC1 with IC50 values of 2.05, 0.93, 1.32, and 4.16 µM, respectively. Further evaluations indicated that C02S could inhibit DNMT and HDAC at cellular levels, thereby inversing mutated methylation and acetylation and increasing expression of tumor suppressor proteins. Moreover, C02S regulated multiple biological processes including inducing apoptosis and G0/G1 cell cycle arrest, inhibiting angiogenesis, blocking migration and invasion, and finally suppressing tumor cells proliferation in vitro and tumor growth in vivo.

Design, synthesis and anticancer evaluation of acridine hydroxamic acid derivatives as dual Topo and HDAC inhibitors.

Multitarget inhibitors design has generated great interest in cancer treatment. Based on the synergistic effects of topoisomerase and histone deacetylase inhibitors, we designed and synthesized a new series of acridine hydroxamic acid derivatives as potential novel dual Topo and HDAC inhibitors. MTT assays indicated that all the hybrid compounds displayed good antiproliferative activities with IC50 values in low micromolar range, among which compound 8c displayed potent activity against U937 (IC50 = 0.90 µM). In addition, compound 8c also displayed the best HDAC inhibitory activity, which was several times more potent than HDAC inhibitor SAHA. Subsequent studies indicated that all the compounds displayed Topo II inhibition activity at 50 µM. Moreover, compound 8c could interact with DNA and induce U937 apoptosis. This study provides a suite of compounds for further exploration of dual Topo and HDAC inhibitors, and compound 8c can be a new dual Topo and HDAC inhibitory anticancer agent.

Synthesis and biological research of novel azaacridine derivatives as potent DNA-binding ligands and topoisomerase II inhibitors.

DNA and DNA-related enzymes are one of the most effective and common used intracellular anticancer targets in clinic and laboratory studies, however, most of DNA-targeting drugs suffered from toxic side effects. Development of new molecules with good antitumor activity and low side effects is important. Based on computer aided design and our previous studies, a series of novel azaacridine derivatives were synthesized as DNA and topoisomerases binding agents, among which compound 9 displayed the best antiproliferative activity with an IC50 value of 0.57µM against U937 cells, which was slightly better than m-AMSA. In addition, compound 9 displayed low cytotoxicity against human normal liver cells (QSG-7701), the IC50 of which was more than 3 times lower than m-AMSA. Later study indicated that all the compounds displayed topoisomerases II inhibition activity at 50µM. The representative compound 9 could bind with DNA and induce U937 apoptosis through the exogenous pathway.

Olaparib hydroxamic acid derivatives as dual PARP and HDAC inhibitors for cancer therapy.

Olaparib was the first PARP inhibitor approved by the FDA for patients with BRCA-mutated ovarian cancer. Recent studies have demonstrated enhanced anticancer effects of combination therapy consisting of olaparib and HDAC inhibitors. Herein, based on rational drug design strategy, hydroxamic acid derivatives of olaparib were constructed as dual PARP and HDAC inhibitors. These hybrid compounds showed potent inhibitory activities against PARP1/2 and HDAC1/6 with IC50 values in the nanomolar range. Furthermore, compound P1 exhibited broad-spectrum antiproliferative activities in selected human cancer cell lines. Specially, P1 showed more potent activity than olaparib and SAHA in cancer cells MDA-MB-231, HCC1937 and Raji, and 4.1-fold less cytotoxicity compared with SAHA to normal cells MCF-10A. Further mechanism study indicated that P1 could induce the cleavage of PARP and the hyperacetylation of histones, increase the expression of DNA damage biomarker γ-H2AX, decrease the level of BRCA1 and RAD51, and regulate tumor cell growth and apoptosis through modulating both mitochondrial- and death receptor-mediated pathways. Therefore, our study suggested that compounds targeting PARP and HDAC concurrently might be a practical approach for cancer therapy.

Exposure of CCRF-CEM cells to acridone derivative 8a triggers tumor death via multiple mechanisms.

A newly synthesized acridone derivative 8a shows potent antitumor activity against CCRF-CEM leukemia cells. Herein, the first proteomic study of 8a effects in CCRF-CEM cells was performed by 2D nano-LC-ESI-MS/MS to better understand the mechanisms of action of 8a. Data analyses based on PLGS, STRING, Cytoscape, and database for annotation, visualization, and integrated discovery identified 55 proteins that were differentially expressed in response to 8a exposure. Multiple cellular pathways were affected, including chromatin organization, energy metabolism, DNA repair, oxidative-stress, and apoptosis. The changes in protein expression were further verified for PKM2. Moreover, 8a lowered down the expression of HEX and PFK-1. Lactate production was decreased in 8a-treated cells, indicating suppression of glycolysis. The elevated XRCC6 and decreased histone expression levels suggested increased DNA damage in 8a-treated cells, which was confirmed by the increased γ-H2AX foci. Molecular docking of 8a with DNA demonstrated direct interactions of 8a with DNA through three hydrogen bonds and four π-π interactions, potentially explaining the mode of action that 8a damaged to DNA. The differential protein profiling and dysfunction of metabolic pathways induced by 8a provide novel insights into the potential action mechanisms of 8a.

Design, synthesis and evaluation of acridine derivatives as multi-target Src and MEK kinase inhibitors for anti-tumor treatment.

Clinical studies have shown enhanced anticancer effects of combined inhibition of Src and MEK kinases. Development of multi-target drugs against Src and MEK is of potential therapeutic advantage against cancers. As a follow-up of our previous studies, and by using molecular docking method, we designed and synthesized a new series of 9-anilinoacridines containing phenyl-urea moieties as potential novel dual Src and MEK inhibitors. The anti-proliferative assays against K562 and HepG-2 tumor cells showed that most of the derivatives displayed good cytotoxicity in vitro. In particular, kinase inhibition assays showed that compound 8m inhibited Src (59.67%) and MEK (43.23%) at 10 µM, and displayed moderate inhibitory activity against ERK and AKT, the downstream effectors of both Src and MEK. Moreover, compound 8m was found to induce K562 cells apoptosis. Structure-activity relationships of these derivatives were analyzed. Our study suggested that acridine scaffold, particularly compound 8m, is of potential interest for developing novel multi-target Src and MEK kinase inhibitors.

Synthesis and biological evaluation of benzimidazole acridine derivatives as potential DNA-binding and apoptosis-inducing agents.

The discovery of new effective DNA-targeted antitumor agent is needed because of their clinical significance. As acridines can intercalate into DNA and benzimidazoles have the ability to bind in the DNA minor groove, a series of novel benzimidazole acridine derivatives were designed and synthesized to be new DNA-targeted compounds. MTT assay indicated that most of the synthesized compounds displayed good antiproliferative activity, among which compound 8l demonstrated the highest activity against both K562 and HepG-2 cells. Further experiments showed that 8l displayed good DNA-binding capability and inhibited topoisomerase I activity. Moreover, compound 8l could induce apoptosis in K562 cell lines through mitochondrial pathway. These data suggested that compound 8l might be potential as new DNA-binding and apoptosis-inducing antitumor agents.

Synthesis and antiproliferative activity of 2,7-diamino l0-(3,5-dimethoxy)benzyl-9(10H)-acridone derivatives as potent telomeric G-quadruplex DNA ligands.

A novel series of l0-(3,5-dimethoxy)benzyl-9(10H)-acridone derivatives with terminal ammonium substituents at C2 and C7 positions on the acridone ring were successfully synthesized as antiproliferation agents. The biologic activity of the acridone compounds against leukemia CCRF-CEM cells demonstrated that some of the compounds displayed good antiproliferative activity, among which compound 6a containing dimethylamine substituents at the terminal C2 and C7 positions exhibited the highest cytotoxicity with IC50 at 0.3µM. In addition compound 6a showed little toxicity against normal 293T cells proliferation with IC50 more than 100µM. Further study indicated that compound 6a had strong binding activity to human telomeric G-quadruplex DNA, as detected by mass spectrometry, CD spectroscopy, UV absorption, FRET and fluorescence quenching assays. Our data suggested that the activity of 6a might be associated with its stabilization of G-quadruplex DNA, which can be developed as potent antitumor agent.

New benzimidazole acridine derivative induces human colon cancer cell apoptosis in vitro via the ROS-JNK signaling pathway.

AIM: To investigate the mechanisms underlying anticancer action of the benzimidazole acridine derivative N-{(1H-benzo[d]imidazol-2-yl)methyl}-2-butylacridin-9-amine(8m) against human colon cancer cells in vitro. METHODS: Human colon cancer cell lines SW480 and HCT116 were incubated in the presence of 8m, and then the cell proliferation and apoptosis were measured. The expression of apoptotic/signaling genes and proteins was detected using RT-PCR and Western blotting. ROS generation and mitochondrial membrane depolarization were visualized with fluorescence microscopy. RESULTS: 8m dose-dependently suppressed the proliferation of SW480 and HCT116 cells with IC50 values of 6.77 and 3.33 µmol/L, respectively. 8m induced apoptosis of HCT116 cells, accompanied by down-regulation of Bcl-2, up-regulation of death receptor-5 (DR5), truncation of Bid, cleavage of PARP, and activation of caspases (including caspase-8 and caspase-9 as well as the downstream caspases-3 and caspase-7). Moreover, 8m selectively activated JNK and p38 without affecting ERK in HCT116 cells. Knockout of JNK1, but not p38, attenuated 8m-induced apoptosis. In addition, 8m induced ROS production and mitochondrial membrane depolarization in HCT116 cells. Pretreatment with the antioxidants N-acetyl cysteine or glutathione attenuated 8m-induced apoptosis and JNK activation in HCT116 cells. CONCLUSION: The new benzimidazole acridine derivative, 8m exerts anticancer activity against human colon cancer cells in vitro by inducing both intrinsic and extrinsic apoptosis pathways via the ROS-JNK1 pathway.

Accumulation characteristics and ecological risk evaluation of microplastics in sediment cores from the artificial reef area and surrounding seas of Haizhou Bay, north China.

One significant "sink" for microplastic (MP) pollution is the sediments. There's a considerable lack of reliable data regarding the historical status of MPs contamination in sediments within marine ranching. In this research, the study area encompassed Haizhou bay marine ranching and adjacent seas. The primary objective was to explore the potential relationships between the accumulation of MPs and both the sample depth and sediment characteristics within the cores. The results unveiled significant contamination of MPs within the sediment cores. The average MPs concentration of sediment was 1.01 ± 1.28 n/g. Fibrous polymers and particles smaller than 1000 µm were frequently found in the sediment. The abundance of MPs exhibited a tendency to decrease with an increase in sediment depth. Artificial reefs and currents affected on MPs distribution in sediment cores. The accumulation of MPs showed a significant correlation (P < 0.05) with the sediment content of different particle sizes, suggesting that the composition of sediment can serve as an indicator of the abundance of MPs. The risk of MP pollution in the sediments of the study area was assessed by establishing a risk assessment model using concentration data of MPs and polymer types. Due to the higher hazard score of polymers (PA and PET) in MPs, the Polymer hazard index (PHI) was elevated to grade II. However, it had a Pollution load index (PLIzone) value of 1.95 (level I). This suggested that contamination was minimal, yet the ecological risk remained relatively high. The ecological risk assessment of MPs served as the foundation for gaining a detailed understanding of the distribution characteristics of MPs. It also furnished essential data support for conducting a comprehensive assessment, developing feasible management strategies, and establishing water quality standards related to plastic waste.

Distribution characteristics and ecological risk assessment of microplastics in intertidal sediments near coastal water.

Plastic products are widely distributed worldwide and continue to have a negative impact on the environment and organisms. Intertidal regions, which interface between upland and marine ecosystems, are regions of high ecological importance and serve as repositories for a variety of plastic wastes. However, ecological risk assessments of microplastics (MPs) in these transitional environments are still scarce. In this study, the morphological characteristics and spatial distribution of MPs in the intertidal surface sediments of Haizhou Bay were analyzed, and an ecological risk assessment framework for MPs was developed. Overall, the average abundance of MPs in the sediments was 2.31 ± 1.35 pieces/g dw. The size of the MPs was mainly less than 1 mm, and the main shape, color and polymer type of the MPs were mainly fibrous (58%), blue (30%), and PVC (22%), respectively. Cluster analyses showed that the sites could be well distinguished by size and polymer type but not by MP shape and color. According to the hazard scores, most of the sites in this area belonged to a risk level of IV, while the pollution loading index (PLI) showed that most of the sites belonged to a risk level of II. The ecological toxicity risk from the species-sensitive distribution (SSD) model showed that one-third of the sites had ecological MPs toxicity risks to marine organisms. We believe that normalized and standardized assessment methods should be implemented to monitor and manage the risk of MPs in the intertidal sediments. Particularly, the multiple dimensions, standard abundance of MPs, as well as MPs ingestion in the intertidal organisms, should be fully considered in the next step.

Developing Air-Stable n-Type SWCNT-Based Composites with High Thermoelectric and Robust Mechanical Properties for Wearable Electronics.

Flexible organic thermoelectric generators are gaining prominence in wearable electronics, leveraging body heat as an energy source. Their advancement is hindered by the scarcity of air-stable n-type organic materials with robust mechanical properties. This study introduces two new polymers (HDCN4 and HDCN8), created through polycondensation of paraformaldehyde and diamine-terminated poly(ethylene glycol) (PEGDA) with molecular weights of 4000 and 8000 g/mol into single-walled carbon nanotubes (SWCNTs). The resulting HDCN4/SWCNT and HDCN8/SWCNT composites show impressive power factors of 225.9 and 108.2 µW m-1 K-2, respectively, and maintain over 90% in air for over four months without encapsulation. The HDCN4/SWCNT composite also demonstrates significant tensile strength (33.2 MPa) and flexibility (up to 10% strain), which is currently the best mechanically n-type thermoelectric material with such a high power factor reported in the literature. A thermoelectric device based on HDCN4/SWCNT generates 4.2 µW of power with a 50 K temperature difference. Additionally, when used in wearable temperature sensors, these devices exhibit high mechanical reliability and a temperature resolution of 0.1 K. This research presents a viable method to produce air-stable n-type thermoelectric materials with excellent performance and mechanical properties.

Observation of electromagnetically induced transparency-like transmission in terahertz asymmetric waveguide-cavities systems.

Electromagnetically induced transparency (EIT)-like transmission was demonstrated in terahertz asymmetric parallel plate waveguides with two identical cavities. By shifting the position of the bottom cavity from the symmetric position in the propagation direction, both the phases of the propagating wave at resonances and the coupling strengths between two cavities are changed, resulting in exciting the additional asymmetric resonance and manipulating the detuning of two different resonant frequencies. The transparent peak between two resonances comes from the cancelation of symmetric and asymmetric resonances. We also use the physical picture of excitation of quasi-dark mode to explain this EIT-like transmission, which is similar to the metamaterial systems.

Novel synthetic acridine derivatives as potent DNA-binding and apoptosis-inducing antitumor agents.

Acridine derivatives have been explored as DNA-binding anticancer agents. Some derivatives show undesired pharmacokinetic properties and new derivatives need to be explored. In this work, a series of novel acridine analogues were synthesized by modifying previously unexplored linkers between the acridine and benzene groups and their antiproliferative activity and the DNA-binding ability were evaluated. Among these derivatives, compound 5c demonstrated DNA-binding capability and topoisomerase I inhibitory activity. In K562 cell lines, 5c induced apoptosis through mitochondria-dependent intrinsic pathways. These data suggested that compound 5c and other acridine derivatives with modified linkers between the acridine and benzene groups might be potent DNA-binding agents.