Alkaline phosphatase-activated prodrug system based on a bifunctional CuO NP tandem nanoenzyme for on-demand bacterial inactivation and wound disinfection.

Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions.

Ladder-Type Redox-Active Polymer Achieves Ultra-stable and Fast Proton Storage in Aqueous Proton Batteries.

Affordable and safe aqueous proton batteries (APBs) with unique "Grotthuss mechanism," are very significant for advancing carbon neutrality initiatives. While organic polymers offer a robust and adaptable framework that is well-suited for APB electrodes, the limited proton-storage redox capacity has constrained their broader application. Herein, a ladder-type polymer (PNMZ) has been designed via a covalent cycloconjugation conformational strategy that exhibits optimized electronic structure and fast intra-chain charge transport within the high-aromaticity polymeric skeleton. As a result, the polymer exhibits exceptional proton-storage redox kinetics, which are evidenced by in-operando monitoring techniques and theoretical calculations. It achieves a remarkable proton-storage capacity of 189 mAh g-1 at 2 A g-1 and excellent long-term cycling stability, with approximately 97.8% capacity retention over 10,000 cycles. Finally, a high-performance all-polymer APB device has been successfully constructed with a desirable capacity retention of 99.7% after 6,000 cycles and high energy density of 56.3 Wh kg-1.

Calmodulin Triggers Activity-Dependent rRNA Biogenesis via Interaction with DDX21.

Protein synthesis in response to neuronal activity, known as activity-dependent translation, is critical for synaptic plasticity and memory formation. However, the signaling cascades that couple neuronal activity to the translational events remain elusive. In this study, we identified the role of calmodulin (CaM), a conserved Ca2+-binding protein, in ribosomal RNA (rRNA) biogenesis in neurons. We found the CaM-regulated rRNA synthesis is Ca2+-dependent and necessary for nascent protein synthesis and axon growth in hippocampal neurons. Mechanistically, CaM interacts with nucleolar DEAD (Asp-Glu-Ala-Asp) box RNA helicase (DDX21) in a Ca2+-dependent manner to regulate nascent rRNA transcription within nucleoli. We further found CaM alters the conformation of DDX21 to liberate the DDX21-sequestered RPA194, the catalytic subunit of RNA polymerase I, to facilitate transcription of ribosomal DNA. Using high-throughput screening, we identified the small molecules batefenterol and indacaterol that attenuate the CaM-DDX21 interaction and suppress nascent rRNA synthesis and axon growth in hippocampal neurons. These results unveiled the previously unrecognized role of CaM as a messenger to link the activity-induced Ca2+ influx to the nucleolar events essential for protein synthesis. We thus identified the ability of CaM to transmit information to the nucleoli of neurons in response to stimulation.

Multi-metal ions co-regulated vanadium oxide cathode toward long-life aqueous zinc-ion batteries.

Interlayer intercalation engineering shows great feasibility to improve the structure stability of the layered oxides. Although high Zn-storage capability has been attained based on the pillar effect of multifarious intercalants, an in-depth understanding the synergistic effect of intercalated multiple metal ions is still in deficiency. Herein, alkali metal ion K+, alkaline earth metal ion Mg2+ and trivalent metal ion Al3+ are introduced into the VO interlayer of V2O5. Due to the different electronegativity and hydrated ion radius of K+, Mg2+ and Al3+, adjusting the relative proportions of these metal ions can achieve an appropriate interlayer spacing, stable layer structure and regular morphology, which facilitates the transport kinetics of Zn2+. Under the synergistic effect of pre-intercalated multi-metal ion, the optimal tri-metal ion intercalated hydrated V2O5 cathode exhibits a high specific capacity of 382.4 mAh g-1 at 0.5 A g-1, and long-term cycling stability with capacity retention of 86 % after 2000 cycles at the high current density of 10 A g-1. Ex-situ and kinetic characterizations reveal the fast charge transfer and reversible Zn2+ intercalation mechanism. The multi-ion engineering strategy provides an effective way to design desirable layered cathode materials for aqueous zinc-ion batteries.

Defect engineering unveiled: Enhancing potassium storage in expanded graphite anode.

Expanded graphite (EG) stands out as a promising material for the negative electrode in potassium-ion batteries. However, its full potential is hindered by the limited diffusion pathway and storage sites for potassium ions, restricting the improvement of its electrochemical performance. To overcome this challenge, defect engineering emerges as a highly effective strategy to enhance the adsorption and reaction kinetics of potassium ions on electrode materials. This study delves into the specific effectiveness of defects in facilitating potassium storage, exploring the impact of defect-rich structures on dynamic processes. Employing ball milling, we introduce surface defects in EG, uncovering unique effects on its electrochemical behavior. These defects exhibit a remarkable ability to adsorb a significant quantity of potassium ions, facilitating the subsequent intercalation of potassium ions into the graphite structure. Consequently, this process leads to a higher potassium voltage. Furthermore, the generation of a diluted stage compound is more pronounced under high voltage conditions, promoting the progression of multiple stage reactions. Consequently, the EG sample post-ball milling demonstrates a notable capacity of 286.2 mAh g-1 at a current density of 25 mA g-1, showcasing an outstanding rate capability that surpasses that of pristine EG. This research not only highlights the efficacy of defect engineering in carbon materials but also provides unique insights into the specific manifestations of defects on dynamic processes, contributing to the advancement of potassium-ion battery technology.

Janus Binder Chemistry for Synchronous Enhancement of Iodine Species Adsorption and Redox Kinetics toward Sustainable Aqueous Zn-I2 Batteries.

Currently, the desired research focus in energy storage technique innovation has been gradually shifted to next-generation aqueous batteries holding both high performance and sustainability. However, aqueous Zn-I2 batteries have been deemed to have great sustainable potential, owing to the merits of cost-effective and eco-friendly nature. However, their commercial application is hindered by the serious shuttle effect of polyiodides during reversible operations. In this work, a Janus functional binder based on chitosan (CTS) molecules was designed and prepared; the polar terminational groups impart excellent mechanical robustness to hybrid binders; meanwhile, it can also deliver isochronous enhancement on physical adsorption and redox kinetics toward I2 species. By feat of highly effective remission to shuttle effect, the CTS cell exhibits superb electrochemical storage capacities with long-term robustness, specifically, 144.1 mAh g-1, at a current density of 0.2 mA g-1 after 1500 cycles. Simultaneously, the undesired self-discharging issue could be also well-addressed; the Coulombic efficiency could remain at 98.8 % after resting for 24 h. More importantly, CTS molecules endow good biodegradability and reusable properties; after iodine species were reloaded, the recycled devices could also deliver specific capacities of 73.3 mAh g-1, over 1000 cycles. This Janus binder provides a potential synchronous solution to realize high comprehensive performance with high iodine utilization and further make it possible for sustainable Zn-I2 batteries.

Electrolyte Chemistry toward Ultrawide-Temperature (-25 to 75 °C) Sodium-Ion Batteries Achieved by Phosphorus/Silicon-Synergistic Interphase Manipulation.

All-weather operation is considered an ultimate pursuit of the practical development of sodium-ion batteries (SIBs), however, blocked by a lack of suitable electrolytes at present. Herein, by introducing synergistic manipulation mechanisms driven by phosphorus/silicon involvement, the compact electrode/electrolyte interphases are endowed with improved interfacial Na-ion transport kinetics and desirable structural/thermal stability. Therefore, the modified carbonate-based electrolyte successfully enables all-weather adaptability for long-term operation over a wide temperature range. As a verification, the half-cells using the designed electrolyte operate stably over a temperature range of -25 to 75 °C, accompanied by a capacity retention rate exceeding 70% even after 1700 cycles at 60 °C. More importantly, the full cells assembled with Na3V2(PO4)2O2F cathode and hard carbon anode also have excellent cycling stability, exceeding 500 and 1000 cycles at -25 to 50 °C and superb temperature adaptability during all-weather dynamic testing with continuous temperature change. In short, this work proposes an advanced interfacial regulation strategy targeted at the all-climate SIB operation, which is of good practicability and reference significance.

Interfacial-Confined Isochronous Conversion to Biphasic Selenide Heterostructure with Enhanced Adsorption Behaviors for Robust High-Rate Na-Ion Storage.

Sodium-ion batteries (SIBs) have gradually become one of the most promising energy storage techniques in the current era of post-lithium-ion batteries. For anodes, transitional metal selenides (TMSe) based materials are welcomed choices , owing to relatively higher specific capacities and enriched redox active sites. Nevertheless, current bottlenecks are blamed for their poor intrinsic electronic conductivities, and uncontrollable volume expansion during redox reactions. Given that, an interfacial-confined isochronous conversion strategy is proposed, to prepare orthorhombic/cubic biphasic TMSe heterostructure, namely CuSe/Cu3 VSe4 , through using MXene as the precursor, followed by Cu/Se dual anchorage. As-designed biphasic TMSe heterostructure endows unique hierarchical structure, which contains adequate insertion sites and diffusion spacing for Na ions, besides, the surficial pseudocapacitive storage behaviors can be also proceeded like 2D MXene. By further investigation on electronic structure, the theoretical calculations indicate that biphasic CuSe/Cu3 VSe4 anode exhibits well-enhanced properties, with smaller bandgap and thus greatly improves intrinsic poor conductivities. In addition, the dual redox centers can enhance the electrochemical Na ions storage abilities. As a result, the as-designed biphasic TMSe anode can deliver a reversible specific capacity of 576.8 mAh g-1 at 0.1 A g-1 , favorable Na affinity, and reduced diffusion barriers. This work discloses a synchronous solution toward demerits in conductivities and lifespan, which is inspiring for TMSe-based anode development in SIBs systems.

Entropy-Regulated Cathode with Low Strain and Constraint Phase-Change Toward Ultralong-Life Aqueous Al-Ion Batteries.

During multivalent ions insertion processes, intense electrostatic interaction between charge carriers and host makes the high-performance reversible Al3+ storage remains an elusive target. On account of the strong electrostatic repulsion and poor robustness, Prussian Blue analogues (PBAs) suffer severely from the inevitable and large strain and phase change during reversible Al3+ insertion. Herein, we demonstrate an entropy-driven strategy to realize ultralong life aqueous Al-ion batteries (AIBs) based on medium entropy PBAs (ME-PBAs) host. By multiple redox active centers introduction, the intrinsic poor conductivity can be enhanced simultaneously, resulting in outstanding capabilities of electrochemical Al3+ storage. Meanwhile, the co-occupation at metal sites in PBA frameworks can also increase the M-N bond intensity, which is beneficial for constraining the phase change during consecutive Al3+ reversible insertion, to realize an extended lifespan over 10,000 cycles. Based on the calculation at different operation states, the fluctuation of ME-PBA lattice parameters is only 1.2 %. Assembled with MoO3 anodes, the full cells can also deliver outstanding electrochemical properties. The findings highlight that, the entropy regulation strategy could uncover the isochronous constraint on both strain and phase transition for long-term reversible Al3+ storage, providing a promising design for advanced electrode materials for aqueous multivalent ions batteries.

Hybrid Binder Chemistry with Hydrogen-Bond Helix for High-Voltage Cathode of Sodium-Ion Batteries.

Since sodium-ion batteries (SIBs) have become increasingly commercialized in recent years, Na3V2(PO4)2O2F (NVPOF) offers promising economic potential as a cathode for SIBs because of its high operating voltage and energy density. According to reports, NVPOF performs poorly in normal commercial poly(vinylidene fluoride) (PVDF) binder systems and performs best in combination with aqueous binder. Although in line with the concept of green and sustainable development for future electrode preparation, aqueous binders are challenging to achieve high active material loadings at the electrode level, and their relatively high surface tension tends to cause the active material on the electrode sheet to crack or even peel off from the collector. Herein, a cross-linkable and easily commercial hybrid binder constructed by intermolecular hydrogen bonding (named HPP) has been developed and utilized in an NVPOF system, which enables the generation of a stable cathode electrolyte interphase on the surface of active materials. According to theoretical simulations, the HPP binder enhances electronic/ionic conductivity, which greatly lowers the energy barrier for Na+ migration. Additionally, the strong hydrogen-bond interactions between the HPP binder and NVPOF effectively prevent electrolyte corrosion and transition-metal dissolution, lessen the lattice volume effect, and ensure structural stability during cycling. The HPP-based NVPOF offers considerably improved rate capability and cycling performance, benefiting from these benefits. This comprehensive binder can be extended to the development of next-generation energy storage technologies with superior performance.

Dynamic Li+ Capture through Ligand-Chain Interaction for the Regeneration of Depleted LiFePO4 Cathode.

After application in electric vehicles, spent LiFePO4 (LFP) batteries are typically decommissioned. Traditional recycling methods face economic and environmental constraints. Therefore, direct regeneration has emerged as a promising alternative. However, irreversible phase changes can significantly hinder the efficiency of the regeneration process owing to structural degradation. Moreover, improper storage and treatment practices can lead to metamorphism, further complicating the regeneration process. In this study, a sustainable recovery method is proposed for the electrochemical repair of LFP batteries. A ligand-chain Zn-complex (ZnDEA) is utilized as a structural regulator, with its ─NH─ group alternatingly facilitating the binding of preferential transition metal ions (Fe3+ during charging and Zn2+ during discharging). This dynamic coordination ability helps to modulate volume changes within the recovered LFP framework. Consequently, the recovered LFP framework can store more Li-ions, enhance phase transition reversibility between LFP and FePO4 (FP), modify the initial Coulombic efficiency, and reduce polarization voltage differences. The recovered LFP cells exhibit excellent capacity retention of 96.30% after 1500 cycles at 2 C. The ligand chain repair mechanism promotes structural evolution to facilitate ion migration, providing valuable insights into the targeted ion compensation for environmentally friendly recycling in practical applications.

ROS-mediated anticancer effects of EGFR-targeted nanoceria.

The therapeutic effectiveness of anticancer drugs, including nanomedicines, can be enhanced with active receptor-targeting strategies. Epidermal growth factor receptor (EGFR) is an important cancer biomarker, constitutively expressed in sarcoma patients of different histological types. The present work reports materials and in vitro biomedical analyses of silanized (passive delivery) and/or EGF-functionalized (active delivery) ceria nanorods exhibiting highly defective catalytically active surfaces. The EGFR-targeting efficiency of nanoceria was confirmed by receptor-binding studies. Increased cytotoxicity and reactive oxygen species (ROS) production were observed for EGF-functionalized nanoceria owing to enhanced cellular uptake by HT-1080 fibrosarcoma cells. The uptake was confirmed by TEM and confocal microscopy. Silanized nanoceria demonstrated negligible/minimal cytotoxicity toward healthy MRC-5 cells at 24 and 48 h, whereas this was significant at 72 h owing to a nanoceria accumulation effect. In contrast, considerable cytotoxicity toward the cancer cells was exhibited at all three times points. The ROS generation and associated cytotoxicity were moderated by the equilibrium between catalysis by ceria, generation of cell debris, and blockage of active sites. EGFR-targeting is shown to enhance the uptake levels of nanoceria by cancer cells, subsequently enhancing the overall anticancer activity and therapeutic performance of ceria.

Promoting the healing of methicillin-resistant Staphylococcus aureus-infected wound by a multi-target antimicrobial AIEgen of 6-Aza-2-thiothymine-decorated gold nanoclusters.

The use of conventional antibiotic therapies is in question owing to the emergence of drug-resistant pathogenic bacteria. Therefore, novel, highly efficient antibacterial agents to effectively overcome resistant bacteria are urgently needed. Accordingly, in this work, we described a novel class luminogen of 6-Aza-2-thiothymine-decorated gold nanoclusters (ATT-AuNCs) with aggregation-induced emission property that possessed potent antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA). Scanning electron microscopy was performed to investigate the interactions between ATT-AuNCs and MRSA. In addition, ATT-AuNCs exhibited excellent ROS generation efficiency and could effectively ablate MRSA via their internalization to the cells. Finally, tandem mass tag-labeling proteome analysis was carried out to investigate the differential expression proteins in MRSA strains. The results suggested that ATT-AuNCs killed MRSA cells through altering the expression of multiple target proteins involved in DNA replication, aminoacyl-tRNA synthesis, peptidoglycan and arginine biosynthesis metabolism. Parallel reaction monitoring technique was further used for the validation of these proteome results. ATT-AuNCs could also be served as a wound-healing agent and accelerate the healing process. Overall, we proposed ATT-AuNCs could serve as a robust antimicrobial aggregation-induced emission luminogen (AIEgen) that shows the ability to alter the activities of multiple targets for the elimination of drug-resistant bacteria.

Pearl-Structure-Enhanced NASICON Cathode toward Ultrastable Sodium-Ion Batteries.

Based on the favorable ionic conductivity and structural stability, sodium superionic conductor (NASICON) materials especially utilizing multivalent redox reaction of vanadium are one of the most promising cathodes in sodium-ion batteries (SIBs). To further boost their application in large-scale energy storage production, a rational strategy is to tailor vanadium with earth-abundant and cheap elements (such as Fe, Mn), reducing the cost and toxicity of vanadium-based NASICON materials. Here, the Na3.05 V1.03 Fe0.97 (PO4 )3 (NVFP) is synthesized with highly conductive Ketjen Black (KB) by ball-milling assisted sol-gel method. The pearl-like KB branch chains encircle the NVFP (p-NVFP), the segregated particles possess promoted overall conductivity, balanced charge, and modulated crystal structure during electrochemical progress. The p-NVFP obtains significantly enhanced ion diffusion ability and low volume change (2.99%). Meanwhile, it delivers a durable cycling performance (87.7% capacity retention over 5000 cycles at 5 C) in half cells. Surprisingly, the full cells of p-NVFP reveal a remarkable capability of 84.9 mAh g-1 at 20 C with good cycling performance (capacity decay rate is 0.016% per cycle at 2 C). The structure modulation of the p-NVFP provides a rational design on the superiority of others to be put into practice.

"Pore-Hopping" Ion Transport in Cellulose-Based Separator Towards High-Performance Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have great potential for large-scale energy storage. Cellulose is an attractive material for sustainable separators, but some key issues still exist affecting its application. Herein, a cellulose-based composite separator (CP@PPC) was prepared by immersion curing of cellulose-based separators (CP) with poly(propylene carbonate) (PPC). With the assistance of PPC, the CP@PPC separator is able to operate the cell stably at high voltages (up to 4.95 V). The "pore-hopping" ion transport mechanism in CP@PPC opens up extra Na+ migration paths, resulting in a high Na+ transference number (0.613). The separator can also tolerate folding, bending and extreme temperature under certain circumstances. Full cells with CP@PPC reveal one-up capacity retention (96.97 %) at 2C after 500 cycles compared to cells with CP. The mechanism highlights the merits of electrolyte analogs in separator modification, making a rational design for durable devices in advanced energy storage systems.

An Integrated Design of Electrodes for Flexible Dual-Ion Batteries.

Due to the widespread employment of carbon materials in novel dual-ion batteries (DIBs) with high energy density, they possess the potential for large-scale energy storage and are inexpensive and environmentally friendly. However, drawbacks such as Al current collector corrosion and significant self-weight, as well as lithium metal abuse and poor deposition reversibility, impair the energy density and cycle performance of lithium-graphite DIBs (Li-G DIBs), severely limiting their application potential. Therefore, an integrated electrode structure design was proposed. That is, the flexible graphite and single-walled carbon nanotubes (SWCNTs) composite cathode (GSC), which is light-weight and self-supporting, and the self-supporting lithium metal anode, which is loaded on the flexible carbon cloth (CC) derived from waste mask (Li@CC), were prepared. Not only were the impacts of current collector corrosion and active material exfoliation avoided on the electrochemical performance, but the areal loading of Li metal was also regulated and its reversibility of deposition enhanced. At a current density of 200 mA g-1 , the constructed Li@CC//GSC full cell could release a specific capacity of 100.5 mAh g-1 , and the capacity retention rate after 300 cycles was greater than 80 %. Moreover, the fabricated flexible Li@CC//GSC full cell is not only recyclable and produces less environmental pollution but also has potential applications in wearable devices.

Advanced flame-retardant electrolyte for highly stabilized K-ion storage in graphite anode.

Although graphite anodes operated with representative de/intercalation patterns at low potentials are considered highly desirable for K-ion batteries, the severe capacity fading caused by consecutive reduction reactions on the aggressively reactive surface is inevitable given the scarcity of effective protecting layers. Herein, by introducing a flame-retardant localized high-concentration electrolyte with retentive solvation configuration and relatively weakened anion-coordination and non-solvating fluorinated ether, the rational solid electrolyte interphase characterized by well-balanced inorganic/organic components is tailored in situ. This effectively prevented solvents from excessively decomposing and simultaneously improved the resistance against K-ion transport. Consequently, the graphite anode retained a prolonged cycling capability of up to 1400cycles (245 mA h g-1, remaining above 12mon) with an excellent capacity retention of as high as 92.4%. This is superior to those of conventional and high-concentration electrolytes. Thus, the optimized electrolyte with moderate salt concentration is perfectly compatible with graphite, providing a potential application prospect for K-storage evolution.

Inorganic nanoparticle-based advanced cancer therapies: Promising combination strategies.

Inorganic nanoparticles for drug delivery in cancer treatment offer many potential advantages because they can maximize therapeutic effect through targeting ligands while minimizing off-target side-effects through drug adsorption and infiltration. Although inorganic nanoparticles were introduced as drug carriers, they have emerged as having the capacity for combined therapeutic capabilities, including anticancer effects through cytotoxicity, suppression of oncogenes and cancer cell signaling pathway inhibition. The most promising advanced strategies for cancer therapy are as synergistic platforms for RNA interference (siRNA, miRNA, shRNA) and as synergistic drug delivery agents for the inhibition of cancer cell signaling pathways. The present work summarizes relevant current work, the promise of which is suggested by a projected compound annual growth rate of âˆ¼ 20% for drug delivery alone.

Anticancer therapeutic effect of cerium-based nanoparticles: known and unknown molecular mechanisms.

Cerium-based nanoparticles (CeNPs), particularly cerium oxide (CeO2), have been studied extensively for their antioxidant and prooxidant properties. However, their complete redox and enzyme-mimetic mechanisms of therapeutic action at the molecular level remain elusive, constraining their potential for clinical translation. Although the therapeutic effects of both antioxidant and prooxidant mechanisms generally are attributed to Ce3+ ↔ Ce4+ redox switching mediation, some studies have hinted at the involvement of unknown pathways in therapeutic effects. While redox switching is recognised increasingly as playing a key role in ROS-dependent cancer therapy, ROS-independent cytotoxicity mechanisms, such as Ce4+ dissolution and autophagy, also are emerging as being of importance. Although ROS-mediated prooxidant therapies are the most intensively studied, particularly in the context of cancer, the antioxidant activity deriving from the redox switching, particularly during radiation therapy, also plays an important role in the protection of normal cells during radiation therapy, hence reducing adverse effects. Since cancer cell proliferation results in aberrant behaviour of the tumour microenvironment (TME), then CeNP-based therapies are being used to address a multiplicity of known and unknown factors that aim to normalise the TME and thus prevent this aberrant behaviour. Although it is perceived that the pH plays a key role in the therapeutic performance of cerium-based nanoparticles, this is not conclusive because the relative importances of other factors, particularly Ce dissolution, Ce3+/Ce4+ ratio, cellular H2O2 level, and the role of anions, remain poorly understood. Consequently, the present work explores these multiple chemistry-driven mechanisms, which are both ROS-dependent and ROS-independent, in cancer therapy.