Biogated mesoporous silica nanoagents for inhibition of cell migration and combined cancer therapy.

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.

Prediction of atrazine degradation in soil based on XGBoost model.

We established the optimal model by using the automatic machine learning method to predict the degradation efficiency of herbicide atrazine in soil, which could be used to assess the residual risk of atrazine in soil. We collected 494 pairs of data from 49 published articles, and selected seven factors as input features, including soil pH, organic matter content, saturated hydraulic conductivity, soil moisture, initial concentration of atrazine, incubation time, and inoculation dose. Using the first-order reaction rate constant of atrazine in soil as the output feature, we established six models to predict the degradation efficiency of atrazine in soil, and conducted comprehensive analysis of model performance through linear regression and related evaluation indicators. The results showed that the XGBoost model had the best performance in predicting the first-order reaction rate constant (k). Based on the prediction model, the feature importance ranking of each factor was in an order of soil moisture > incubation time > pH > organic matter > initial concentration of atrazine > saturated hydraulic conductivity > inoculation dose. We used SHAP to explain the potential relationship between each feature and the degradation ability of atrazine in soil, as well as the relative contribution of each feature. Results of SHAP showed that time had a negative contribution and saturated hydraulic conductivity had a positive contribution. High values of soil moisture, initial concentration of atrazine, pH, inoculation dose and organic matter content were generally distributed on both sides of SHAP=0, indicating their complex contributions to the degradation of atrazine in soil. The XGBoost model method combined with the SHAP method had high accuracy in predicting the performance and interpretability of the k model. By using machine learning method to fully explore the value of historical experimental data and predict the degradation efficiency of atrazine using environmental parameters, it is of great significance to set the threshold for atrazine application, reduce the residual and diffusion risks of atrazine in soil, and ensure the safety of soil environment.

Ultralow Background Membrane Editors for Spatiotemporal Control of Phosphatidic Acid Metabolism and Signaling.

Phosphatidic acid (PA) is a multifunctional lipid with important metabolic and signaling functions, and efforts to dissect its pleiotropy demand strategies for perturbing its levels with spatiotemporal precision. Previous membrane editing approaches for generating local PA pools used light-mediated induced proximity to recruit a PA-synthesizing enzyme, phospholipase D (PLD), from the cytosol to the target organelle membrane. Whereas these optogenetic PLDs exhibited high activity, their residual activity in the dark led to undesired chronic lipid production. Here, we report ultralow background membrane editors for PA wherein light directly controls PLD catalytic activity, as opposed to localization and access to substrates, exploiting a light-oxygen-voltage (LOV) domain-based conformational photoswitch inserted into the PLD sequence and enabling their stable and nonperturbative targeting to multiple organelle membranes. By coupling organelle-targeted LOVPLD activation to lipidomics analysis, we discovered different rates of metabolism for PA and its downstream products depending on the subcellular location of PA production. We also elucidated signaling roles for PA pools on different membranes in conferring local activation of AMP-activated protein kinase signaling. This work illustrates how membrane editors featuring acute, optogenetic conformational switches can provide new insights into organelle-selective lipid metabolic and signaling pathways.

ZnMo-MOF as anti-CO hydrogen electrocatalyst enhance microbial electrosynthesis for CO/CO2 conversion.

Microbial electrosynthesis (MES) is an electrically driven technology that can be used for converting CO/CO2 into chemicals. The unique electronic and substrate properties of CO make it an important research target for MES. However, CO can poison the cathode and increase the overpotential of hydrogen evolution reaction (HER), thus reducing the electron transfer rate via H2. This work evaluated the effect of an anti-CO HER catalyst on the performance of MES for CO/CO2 conversion. ZnMo-metal-organic framework (MOF) materials with different calcination temperatures were synthesized. ZnMo-MOF-800 with Mo2C nanoparticles as active centers exhibited excellent resistance to CO toxicity. It also obtained the highest hydrogen evolution and enhanced electron transfer rate in CO atmosphere. MES with ZnMo-MOF-800 cathode and Clostridium ljungdahlii as biocatalyst obtained 0.31 g L-1 d-1 acetate yield, 0.1 g L-1 d-1 butyrate yield, and 0.09 g L-1 d-1 2,3-butanediol yield in CO/CO2, while Pt/C only get 0.076 g L-1 d-1 acetate yield, 0.05 g L-1 d-1 butyrate yield and 0.02 g L-1 d-1 2,3-butanediol yield. ZnMo-MOF-800 was conducive to biofilm formation, enabling it to better resist CO toxicity. This work provides new opportunities for constructing a highly efficient cathode with an anti-CO hydrogen evolution catalyst to enhance CO/CO2 conversion in MES.

Core-shell "loading-type" nanomaterials enabling glucometer readout for portable and sensitive detection of p-aminophenol in real samples.

A one-target-many-trigger signal model sensing strategy is proposed for quickly, sensitive and on-site detection of the environmental pollutant p-aminophenol (PAP) by use of a commercial personal glucose meter (PGM) for signal readout with the core-shell "loading-type" nanomaterial MSNs@MnO2 as amplifiable nanoprobes. In this design, the mesoporous silica nanoparticles (MSNs) nanocontainer with entrapped signal molecule glucose is coated with redoxable manganese dioxide (MnO2) nanosheets to form the amplifiable nanoprobes (Glu-MSNs@MnO2). When encountered with PAP, the redox reaction between the MnO2 and PAP can induce the degradation of the outer layer of MSNs@MnO2, liberating multiple copies of the loaded glucose to light up the PGM signal. Owing to the high loading capability of nanocarriers, a "one-to-many" relationship exists between the target and the signal molecule glucose, which can generate adequate signal outputs to achieve the requirement of on-site determination of environmental pollutants. Taking advantage of this amplification mode, the developed PAP assay owns a dynamic linear range of 10.0-400 µM with a detection limit of 2.78 µM and provides good practical application performance with above 96.7 ± 4.83% recovery in environmental water and soil samples. Therefore, the PGM-based amplifiable sensor for PAP proposed can accommodate these requirements of environment monitoring and has promising potential for evaluating pollutants in real environmental samples.

A Dual Functional Fluorescent Probe Based on Phenothiazine for Detecting Hg2+ and ClO- and its Applications.

For the efficient detection of Hg2+ and ClO-, a double-analyte-responsive fluorescent probe PTB was successfully synthesized by combining N-butyl-3-formyl phenothiazine with hydrazine benzothiazole, and designing a specific reaction site for recognizing two analytes (Hg2+ and ClO-) in a compound. It was shown that probe PTB successfully formed a stable complex with Hg2+ in the coordination ratio of 2:1 by using the strong sulfur affinity of Hg2+, which resulted in a remarkable "turn-off" effect, with a quenching efficiency of 92.5% and four reversible cycles of Hg2+ fluorescence detection. For the fluorescence detection of Hg2+, the response time is fast (≤ 2 min) and the detection limit is low (7.8 nM), showing extremely high sensitivity, and the performance is obviously better than that of the reported fluorescent probes for detecting Hg2+. In particular, probe PTB has low toxicity and good biocompatibility, and has been successfully used for imaging of Hg2+ in living cells. Moreover, probe PTB uses thioether bond and carbon-nitrogen double bond as reaction sites to detect ClO-, which has large Stokes Shift (149 nm), good selectivity, high quenching efficiency (96.5%) and fast time response (about 10 s), and successfully detects ClO- in actual water samples. The dual functional fluorescent probe PTB is sensitive for Hg2+ and ClO-. It has been successfully used for making pH fluorescent test paper and imaging detection of exogenous Hg2+ in VSMC cells with low toxicity.

Ultralow background membrane editors for spatiotemporal control of lipid metabolism and signaling.

Phosphatidic acid (PA) is a multifunctional lipid with important metabolic and signaling functions, and efforts to dissect its pleiotropy demand strategies for perturbing its levels with spatiotemporal precision. Previous membrane editing approaches for generating local PA pools used light-mediated induced proximity to recruit a PA-synthesizing enzyme, phospholipase D (PLD), from the cytosol to the target organelle membrane. Whereas these optogenetic PLDs exhibited high activity, their residual activity in the dark led to undesired chronic lipid production. Here, we report ultralow background membrane editors for PA wherein light directly controls PLD catalytic activity, as opposed to localization and access to substrates, exploiting a LOV domain-based conformational photoswitch inserted into the PLD sequence and enabling their stable and non-perturbative targeting to multiple organelle membranes. By coupling organelle-targeted LOVPLD activation to lipidomics analysis, we discovered different rates of metabolism for PA and its downstream products depending on the subcellular location of PA production. We also elucidated signaling roles for PA pools on different membranes in conferring local activation of AMP-activated protein kinase signaling. This work illustrates how membrane editors featuring acute, optogenetic conformational switches can provide new insights into organelle-selective lipid metabolic and signaling pathways.

Two novel fluorescent probes based on quinolinone for continuous recognition of Al3+ and ClO.

On the basis of classical Schiff base reaction, two novel and efficient fluorescent probes (DQNS, DQNS1) were designed and synthesized by introducing Schiff base structure into dis-quinolinone unit for structural modification, which can be used to detect Al3+ and ClO-. Because the power supply capacity of H is weaker than that of methoxy, DQNS shows better optical performance: a large Stokes Shift (132 nm), identify Al3+ and ClO- with high sensitivity and selectivity, low detection limit (29.8 nM and 25 nM) and fast response time (10 min and 10 s). Through the working curve and NMR titration experiment, the recognition mechanism of Al3+ and ClO- (PET and ICT) probes are confirmed. Meanwhile, it is speculated that the probe has continuity for the detection of Al3+ and ClO-. Furthermore, DQNS detection of Al3+ and ClO- was applied to real water samples and living cell imaging.

Self-powered DNA nanomachines for fluorescence detection of lead.

A versatile DNA nanomachine detection system has been developed via the combination of DNAzyme with catalytic hairpin assembly (CHA) technology for achieving accurate and sensitive detection of lead ions (Pb2+). In the presence of target Pb2+, capture DNA nanomachine formed by AuNP and DNAzyme recognized and reacted with Pb2+, which yielded an "active" DNAzyme, that induced the cleavage of substrate strand, and then released the initiator DNA (TT) for CHA. With the help of the initiator DNA TT, self-powered CHA was activated to achieve the signal amplification reaction in the detection of DNA nanomachine. Meanwhile, the initiator DNA TT was released and hybridized with the other H1 strand to initiate another CHA, replacement, and turnovers, producing enhanced fluorescence signal of fluorophore FAM (excitation 490 nm/emission 520 nm) for sensitive determination of Pb2+. Under the optimized conditions, the DNA nanomachine detection system revealed high selectivity toward Pb2+ in the concentration range 50-600 pM, with the limit of detection (LOD) of 31 pM. Recovery tests demonstrated that the DNA nanomachine detection system has excellent detection capability in real samples. Therefore, the proposed strategy can be extended and act as a basic platform for highly accurate and sensitive detection of various heavy metal ions.

DNA-Programed Plasmon Rulers Decrypt Single-Receptor Dimerization on Cell Membrane.

Decrypting the dynamics of receptor dimerization on cell membranes bears great importance in identifying the mechanisms regulating diverse cellular activities. In this regard, long-term monitoring of single-molecule behavior during receptor dimerization allows deepening insight into the dimerization process and tracking of the behavior of individual receptors, yet this remains to be realized. Herein, real-time observation of the receptor tyrosine kinases family (RTKs) at single-molecule level based on plasmon rulers was achieved for the first time, which enabled precise regulation and dynamic monitoring of the dimerization process by DNA programming with excellent photostability. Additionally, those nanoprobes demonstrated substantial application in the regulation of RTKs protein dimerization/phosphorylation and activation of downstream signaling pathways. The proposed nanoprobes hold considerable potential for elucidating the molecular mechanisms of single-receptor dimerization as well as the conformational transitions upon dimerization, providing a new paradigm for the precise manipulation and monitoring of specific single-receptor crosslink events in biological systems.

Photothermally Triggered Copper Payload Release for Cuproptosis-Promoted Cancer Synergistic Therapy.

Cuproptosis is a new form of programmed cell death and exhibits enormous potential in cancer treatment. However, reducing the undesirable Cu ion release in normal tissue and maximizing the copper-induced therapeutic effect in cancer sites are two main challenges. In this study, we constructed a photothermally triggered nanoplatform (Au@MSN-Cu/PEG/DSF) to realize on-demand delivery for synergistic therapy. The released disulfiram (DSF) chelated with Cu2+ in situ to generate highly cytotoxic bis(diethyldithiocarbamate)copper (CuET), causing cell apoptosis, and the formed Cu+ species promoted toxic mitochondrial protein aggregation, leading to cell cuproptosis. Synergistic with photothermal therapy, Au@MSN-Cu/PEG/DSF could effectively kill tumor cells and inhibit tumor growth (inhibition rate up to 80.1 %). These results provide a promising perspective for potential cancer treatment based on cuproptosis, and may also inspire the design of advanced nano-therapeutic platforms.

MnO2-DNA nanomaterials toward the dual signal detection of P-aminophenol micropollutants.

P-Aminophenol (PAP), a potentially toxic and mutagenic compound, is widely distributed in water and soil and has serious side effects on human health. This study presents a convenient, sensitive, and effective dual-signal assay for the detection of PAP in the environment. Two-dimensional manganese dioxide (MnO2) nanosheets were used as the carrier and quencher for fluorophore-labelled DNA to form a dual-signal nanoprobe, MnO2-DNA. Based on a specific redox reaction between the MnO2 nanosheets and target PAP, the corresponding absorption intensity of the product and the fluorescence intensity were both "turn-on" and also exhibited excellent correlation with the concentration of PAP. This strategy not only remarkably simplifies the detection process but also improves the reliability of results due to the dual-signal response, which has promising applications in environmental, clinical, and industrial research fields.

A super large Stokes shift ratiometric fluorescent probe for highly selective sensing of ClO- in bio-imaging and real water samples.

Based on the fluorescence resonance energy transfer (FRET), a ratiometric fluorescent probe (NQ) was successfully designed and synthesized, in which quinolinone moiety was selected as the energy donor and naphthalimide block as the energy acceptor. NQ has a super large Stokes shift (231 nm) and a big quantum yield (0.463). Compared with previously reported probes with similar recognition sites, NQ can high sensitively and selectively recognize ClO- with a much low limit of detection (LOD = 21 nM) and extremely rapid response time (20 s). NQ has a strong anti-interference effect and a color change in the solution which can be seen by the "naked eye". Moreover, NQ can be applied to detect ClO- in real water samples and living cells imaging.

Network Analysis Reveals the Combination of Controlled-Release and Regular Urea Enhances Microbial Interactions and Improves Maize Yields.

Increased complexity of microbial networks can contribute to increased biodiversity and multifunctionality and thus crop productivity. However, it is not clear which combination ratio of regular and controlled-release urea will increase the soil microbial community complexity and improve maize yield in the North China Plain. To address this knowledge gap, a 2-year field experiment was conducted to explore the effects of the combination of regular (U) and controlled release (S) urea ratios [no fertilizer control (CT), regular urea alone (U), controlled-release urea alone (S), controlled-release urea mixed with regular urea 3:7 (SU3), controlled-release urea mixed with regular urea 5:5 (SU5), and controlled-release urea mixed with regular urea 7:3 (SU7)] on XianYu 688 yield and its rhizosphere and bulk soil microbial community composition and network complexity at different fertility stages. The combination of controlled-release and regular urea increased the N agronomic efficiency, N partial factors productivity, maize yield, and grain number per spike, with the maximum maize yield (9,186 kg ha-1) being achieved when the ratio of controlled-release urea to regular urea was 3:7 (SU3, p < 0.05). Maize yield increased by 13% in the SU3 treatment compared to the CT treatment. Rhizosphere soil microbial diversity remained stable at the silking stage of maize while increased at the physiological maturity stage of maize, with the increasing controlled-release to regular N fertilizer ratios (from 3:7 to 7:3, p < 0.05). This result suggests that a combination of regular and controlled-release N fertilizer can still substantially increase soil microbial diversity in the later stages of maize growth. The combination of controlled-release and regular urea is more effective in improving microbial network total links and average degree, and N agronomic efficiency (R 2 = 0.79, p < 0.01), N partial factor productivity (R 2 = 0.79, p < 0.01), spikes per unit area (R 2 = 0.54, p < 0.05), and maize yield (R 2 = 0.42, p < 0.05) increased with the microbial network complexity. This result indicates that the higher microbial network complexity is strongly associated with the higher N agronomic efficiency and N partial factors productivity and maize yield. In conclusion, the ratio of controlled-release to regular urea at SU3 not only increases the yield of maize and N agronomic efficiency but also enhances microbial diversity and network complexity in the North China Plain.

A reversible plasmonic nanoprobe for dynamic imaging of intracellular pH during endocytosis.

Understanding the pH evolution during endocytosis is essential for our comprehension of the fundamental processes of biology as well as effective nanotherapeutic design. Herein, we constructed a plasmonic Au@PANI core-shell nanoprobe, which possessed significantly different scattering properties under acidic and basic conditions. Encouragingly, the scattering signal of Au@PANI nanoprobes displayed a positive linear correlation with the pH value not only in PBS but also in nigericin-treated cells. Ultimately, benefiting from the excellent response properties as well as the excellent biocompatibility and stability, the Au@PANI nanoprobes have successfully enabled a dynamic assessment of the evolving pH in the endosomal package as the endosome matured from early to late, and eventually to the lysosome, by reporting scattering signal changes.

A plasmonic Au-Ag janus nanoprobe for monitoring endogenous hydrogen sulfide generation in living cells.

Hydrogen sulfide (H2S) is an essential intracellular gasotransmitter undertaking numerous signaling roles and physiological effects. Herein, an ingenious anisotropic gold (Au)-silver (Ag) Janus plasmonic nanoprobe was constructed based on the dark-field light scattering imaging for the detection of exogenous and endogenous H2S. In the presence of sulfide, the Ag islands as the sensing agent were susceptible to oxidation to Ag2S, which induced changes in the longitudinal localized surface plasmon resonance (LSPR) properties of Au-Ag Janus nanoparticles (JNPs), resulting in remarkable and distinctive scattering color changes as well as spectral shifts. The JNPs exhibited satisfying anti-interference capability and a good linear relationship with a low detection limit of 0.11 nM. Additionally, this distinct nanoprobe was successfully applied to monitor endogenous H2S as well as map local variations of H2S in real-time with its unique intuition and sensitivity in intracellular imaging applications. This work provided a promising application in the plasmonic detection of intracellular H2S and paved insight into the H2S-related biological process.

Core-shell "loading-type" nanomaterials towards: Simultaneous imaging analysis of glutathione and microRNA.

A novel type of core-shell "loading-type" nanomaterials, which integrated excellent biocompatibility, high loading capacity, efficient delivery, dual target recognition and response all-in-one, was fabricated for simultaneous imaging analysis of glutathione and microRNAs in living cells. Specifically, the core-shell "loading-type" nanomaterials (termed as MSNs@MnO2) were formed with mesoporous silica nanoparticles (MSNs) as core and a two-dimensional manganese dioxide nanosheets (MnO2) as outer layer. Based on the excellent loading capability, the core MSNs was utilized as carriers for signal molecules of rhodamine 6G (R6G). Meanwhile, the shell MnO2 acted as carriers for nucleic acid compounds, the locker for blocking R6G in the pore of MSNs, and reactant for reacting with redox species. Upon entering the cells, the specific redox reaction between the MnO2 nanosheets and cellular glutathione (GSH) induced the removal of the locker layer from the MSNs, thereby triggering unlocking, releasing, and recovering the corresponding fluorescence of R6G. While encounter with miRNAs, the molecular beacons (MB) adsorbed on the MnO2 nanosheets hybridized with target miRNA, which induced the conformational transition of the hairpin molecules, formed new secondary structures, and then recovered the fluorescence signal. Due to the each recovered fluorescence intensity was correlated with the corresponding target molecules, simultaneous detection of dual biomarkers was successfully achieved via the core-shell "loading-type" nanomaterials, which can provide more precise data guidance for diagnosis and disease treatment, and also own promising application in such research area.

Responses of photosynthesis, antioxidant enzymes, and related gene expression to nicosulfuron stress in sweet maize (Zea mays L.).

Weed control in maize (Zea mays L.) crops is usually undertaken using the postemergence herbicide nicosulfuron. The toxicity of nicosulfuron on maize, especially sweet maize, has been widely reported. In order to examine the effect of nicosulfuron on seedling photosynthetic characteristics, chlorophyll fluorescence, reactive oxygen species production, antioxidant enzyme activities, and gene expressions on sweet maize, nicosulfuron-tolerant "HK310" and nicosulfuron-sensitive "HK320" were studied. All experiment samples were subjected to a water or 80 mg kg-1 of nicosulfuron treatment when sweet maize seedlings grow to the stage of four leaves. After treatment with nicosulfuron, results for HK301 were significantly higher than those for HK320 for net photosynthetic rate, transpiration rate, stomatal conductance, leaf maximum photochemical efficiency of PSII, photochemical quenching of chlorophyll fluorescence, and the electron transport rate. These results were contrary to nonphotochemical quenching and intercellular CO2 concentration. As exposure time increased, associated effects also increased. Both O2·- and H2O2 detoxification is modulated by antioxidant enzymes. Compared to HK301, SOD, POD, and CAT activities of HK320 were significantly reduced as exposure time increase. Compared to HK320, the gene expression for the majority of SOD genes, except for SOD2, increased due to inducement by nicosulfuron, and it significantly upregulated the gene expression of CAT in HK301. Results from this study indicate that plants can improve photosynthesis, scavenging capabilities of ROS, and protective mechanisms to alleviate phytotoxic effect of nicosulfuron. Future research is needed to further elucidate the important role antioxidant systems and gene regulation play in herbicide detoxification in sweet maize.

Role of bioaerosol in virus transmission and material-based countermeasures.

Respiratory pathogens transmit primarily through particles such as droplets and aerosols. Although often overlooked, the resuspension of settled droplets is also a key facilitator of disease transmission. In this review, we discuss the three main mechanisms of aerosol generation: direct generation such as coughing and sneezing, indirect generation such as medical procedures, and resuspension of settled droplets and aerosols. The size of particles and environmental factors influence their airborne lifetime and ability to cause infection. Specifically, humidity and temperature are key factors controlling the evaporation of suspended droplets, consequently affecting the duration in which particles remain airborne. We also suggest material-based approaches for effective prevention of disease transmission. These approaches include electrostatically charged virucidal agents and surface coatings, which have been shown to be highly effective in deactivating and reducing resuspension of pathogen-laden aerosols.

Core-Shell Plasmonic Nanomaterials toward: Dual-Mode Imaging Analysis of Glutathione and Enhanced Chemodynamic Therapy.

A simple process, rich information, and intelligent response are the goals pursued by cancer diagnosis and treatment. Herein, we developed a core-shell plasmonic nanomaterial (Au@MnO2-DNA), which consisted of a AuNP core with an outer shell MnO2 nanosheet decorated with fluorophore modified DNA, to achieve the aforementioned aims. On the basis of the unique optical properties of plasmonic nanoparticles and the oxidability of the shell MnO2, scattering signal and fluorescence (FL) signal changes were both related to the expression level of glutathione (GSH), for which a dual-mode imaging analysis was successfully achieved on single optical microscope equipment with one-key switching. Meanwhile, the product of Mn2+ from the reaction between MnO2 and GSH not only served as a smart chemodynamic agent to initiate Fenton-like reaction for achieving chemodynamic therapy (CDT) of cancer cells but also relieved the side effect of intracellular GSH in cancer therapy. Therefore, the core-shell plasmonic nanomaterials with dual modal switching features and diagnostic properties act as excellent probes for achieving bioanalysis of aberrant levels of intracellular GSH and simultaneously activating the CDT of cancer cells based on the in situ reactions in cancer cells.