Cassava phosphatase PP2C1 modulates thermotolerance via fine-tuning dephosphorylation of antioxidant enzymes.

Global warming is an adverse environmental factor that threatens crop yields and food security. 2C-type protein phosphatases (PP2Cs), as core protein phosphatase components, play important roles in plant hormone signaling to cope with various environmental stresses. However, the function and underlying mechanism of PP2Cs in the heat stress response remain elusive in tropical crops. Here, we report that MePP2C1 negatively regulated thermotolerance in cassava (Manihot esculenta Crantz), accompanied by the modulation of reactive oxygen species (ROS) accumulation and the underlying antioxidant enzyme activities of catalase (CAT) and ascorbate peroxidase (APX). Further investigation found that MePP2C1 directly interacted with and dephosphorylated MeCAT1 and MeAPX2 at serine (S) 112 and S160 residues, respectively. Moreover, in vitro and in vivo assays showed that protein phosphorylation of MeCAT1S112 and MeAPX2S160 was essential for their enzyme activities, and MePP2C1 negatively regulated thermotolerance and redox homeostasis by dephosphorylating MeCAT1S112 and MeAPX2S160. Taken together, this study illustrates the direct relationship between MePP2C1-mediated protein dephosphorylation of MeCAT1 and MeAPX2 and ROS accumulation in thermotolerance to provide insights for adapting to global warming via fine-tuning thermotolerance of the tropical crop cassava.

NF-YC15 transcription factor activates ethylene biosynthesis and improves cassava disease resistance.

The nuclear factor Y (NF-Y) transcription factors play important roles in plant development and physiological responses. However, the relationship between NF-Y, plant hormone and plant stress resistance in tropical crops remains unclear. In this study, we identified MeNF-YC15 gene in the NF-Y family that significantly responded to Xanthomonas axonopodis pv. manihotis (Xam) treatment. Using MeNF-YC15-silenced and -overexpressed cassava plants, we elucidated that MeNF-YC15 positively regulated disease resistance to cassava bacterial blight (CBB). Notably, we illustrated MeNF-YC15 downstream genes and revealed the direct genetic relationship between MeNF-YC15 and 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase (MeACO1)-ethylene module in disease resistance, as evidenced by the rescued disease susceptibility of MeNF-YC15 silenced cassava plants with ethylene treatment or overexpressing MeACO1. In addition, the physical interaction between 2C-type protein phosphatase 1 (MePP2C1) and MeNF-YC15 inhibited the transcriptional activation of MeACO1 by MeNF-YC15. In summary, MePP2C1-MeNF-YC15 interaction modulates ethylene biosynthesis and cassava disease resistance, providing gene network for cassava genetic improvement.

FoxA2 represses ERß-mediated pyroptosis in endometriosis by transcriptionally inhibiting IGF2BP1.

BACKGROUND: Endometriosis is a severe disease which is associated with excessive activation of pyroptosis. Our present research aimed to investigate the function of Forkhead Box A2 (FoxA2) in regulating pyroptosis in endometriosis. METHODS: IL-1ß and IL-18 concentrations were assessed using ELISA. Cell pyroptosis was analyzed using flow cytometry. TUNEL staining was performed to determine human endometrial stromal cells (HESC) death. Moreover, ERß mRNA stability was assessed using RNA degradation assay. Finally, the binding relationships between FoxA2, IGF2BP1 and ERß were verified by dual-luciferase reporter system, ChIP, RIP and RNA pull-down assays. RESULTS: Our results revealed that IGF2BP1 and ERß were significantly upregulated in ectopic endometrium (EC) tissues of endometriosis patients compared to that in eutopic endometrium (EU) tissues as well as IL-18 and IL-1ß levels. Loss-of-function experiments subsequently demonstrated that either IGF2BP1 knockdown or ERß knockdown could repress HESC pyroptosis. In addition, IGF2BP1 upregulation promoted the pyroptosis in endometriosis by binding to ERß and promoting ERß mRNA stability. Our further research displayed that FoxA2 upregulation suppressed HESC pyroptosis by interacting with IGF2BP1 promoter. CONCLUSION: Our research proved that FoxA2 upregulation downregulated ERß by transcriptionally inhibiting IGF2BP1, thereby repressing pyroptosis in endometriosis.

An Aptamer-Based Nanoflow Cytometry Method for the Molecular Detection and Classification of Ovarian Cancers through Profiling of Tumor Markers on Small Extracellular Vesicles.

Molecular profiling of protein markers on small extracellular vesicles (sEVs) is a promising strategy for the precise detection and classification of ovarian cancers. However, this strategy is challenging owing to the lack of simple and practical detection methods. In this work, using an aptamer-based nanoflow cytometry (nFCM) detection strategy, a simple and rapid method for the molecular profiling of multiple protein markers on sEVs was developed. The protein markers can be easily labeled with aptamer probes and then rapidly profiled by nFCM. Seven cancer-associated protein markers, including CA125, STIP1, CD24, EpCAM, EGFR, MUC1, and HER2, on plasma sEVs were profiled for the molecular detection and classification of ovarian cancers. Profiling these seven protein markers enabled the precise detection of ovarian cancer with a high accuracy of 94.2 %. In addition, combined with machine learning algorithms, such as linear discriminant analysis (LDA) and random forest (RF), the molecular classifications of ovarian cancer cell lines and subtypes were achieved with overall accuracies of 82.9 % and 55.4 %, respectively. Therefore, this simple, rapid, and non-invasive method exhibited considerable potential for the auxiliary diagnosis and molecular classification of ovarian cancers in clinical practice.

Chemically Synthetic Membrane Receptors Establish Cells with Artificial Sense-and-Respond Signaling Pathways.

Chemically synthetic receptors that establish cells a new sense-and-respond capability to interact with outer worlds are highly desired, but rarely reported. In this work, we develop a membrane-anchored synthetic receptor (Ts-pHLIP-Pr) using DNA and peptide as the building block to equip cells with artificial signaling pathways. Upon sensing external pH stimuli, the Pr module can be translocated across the cell membrane via the conformation switch of pHLIP, enabling membrane-proximal recruitment of specific proteins to trigger downstream signaling cascades. Our experimental results demonstrate the capability of Ts-pHLIP-Pr for regulating PKCε-related signaling events upon responding to external pH reduction. With a modular feature, this receptor can be extended to elicit T cell activation through low-pH environment-induced directional movement of cytoplasmic ZAP70. Our work is expected to offer a new paradigm for intelligent synthetic biology and customized cell engineering.

Multicolor Adjustable B-N Molecular Switches: Simple, Efficient, Portable, and Visual Identification of Butanol Isomers.

As intelligent probes, dynamic and controllable molecular switches are useful tools for probing and intervening in life processes. However, the types and properties of molecular switches are still relatively single and often can only make two actions: "off" and "on". Therefore, the development of novel molecular switches with multiple colors and multiple instructions is very challenging. Herein, we propose a novel strategy based on the instability of the Lewis acid-base pair (boron (B) and nitrogen (N)), such as introducing the Schiff base (C═N) group into the aminoborane skeleton and preparing the novel molecular switches BN-HDZ and BN-HDZ-N. These two molecules were found to have good multicolor fluorescence switching capability for methanol. Surprisingly, the compound BN-HDZ-N shows unprecedented visual identification for the butanol isomers and could be made into a portable strip for simple and rapid visual identification of the four isomers of butanol, promising an alternative to conventional Lucas reagents. This provides a novel strategy for the design and fabrication of novel multicolor-tunable molecular switches with visual identification of isomers.

CuI-p-DPA coordination polymer isomers for "turn-on" fluorescence detection of thiophanate-methyl.

Three copper iodide coordination polymer (CuI-p-DPA) isomers were prepared from the fluorescent organic ligand p-DPA and cuprous iodide (CuI) under different solvothermal conditions, which exhibited quenched fluorescence behaviors after forming coordination polymers (CPs). These CuI-p-DPA isomers showed discrepant fluorescence responses to thiophanate-methyl (TM). Among these CuI-p-DPA isomers, α-CuI-p-DPA exhibited the maximum fluorescence enhancement after its incubation with TM in aqueous solution. The fluorescence enhancement mechanism was that TM competed with the ligand p-DPA to coordinate with CuI clusters, and then α-CuI-p-DPA released p-DPA into the solution and induced fluorescence enhancement. The present detection method possesses the advantages of good selectivity, high sensitivity, short response time, and strong anti-interference ability with a linear range of 0.5-100 µM and a detection limit of 0.01 µM. This study not only reveals that the spatial structures of CPs play an important role in the fluorescence response ability, but also provide a new fluorescence signal-on analysis method to rapidly and sensitively determine the pesticide residue for TM.

Stellate ganglion block suppresses hippocampal ferroptosis to attenuate cerebral ischemia-reperfusion injury via the Hippo pathway.

Ischemic stroke is a disabling and fatal disease caused by the insufficient blood supply to the brain. Stellate ganglion block (SGB) is a type of anesthesia commonly used to relieve pain. Here, we sought to identify the effects of SGB on cerebral ischemia-reperfusion (I/R) injury. The middle cerebral artery occlusion (MCAO) model was established in rats. The brain injury was assessed using the 2,3,5-triphenyl-tetrazolium-chloride (TTC) staining assay and neurological score. Ferroptosis was analyzed by detecting cell death, Fe2+ content, glutathione (GSH), malonic dialdehyde (MDA), superoxide dismutase (SOD), and ferroptosis-related factors. The mechanisms of SGB were assessed using the western blot. The results showed that I/R increased brain infarction and damaged neurological function. SGB decreased I/R-induced infarction and improved neurological function. Meantime, SGB inhibited ferroptosis of the hippocampus induced by I/R via the Hippo pathway. and the Yes1 associated transcriptional regulator (YAP) of this pathway was positively correlated with the ferroptosis-related solute carrier family 7 member 11 (SLC7A11). Inhibition of the Hippo pathway reversed the effects of SGB on brain injury and ferroptosis. In conclusion, SGB inhibited ferroptosis of hippocampal neurons via activating the Hippo pathway and thereby alleviated I/R injury. The data provide a novel insight into the treatment of ischemic stroke and even other ischemic encephalopathies.

Efficacy and mechanism of stellate ganglion block in patients undergoing carotid endarterectomy.

OBJECTIVES: Carotid endarterectomy (CEA) is an effective technique for carotid artery stenosis and has been widely used. Stellate ganglion block (SGB) has good effect on the treatment of both painful and non-painful diseases. To investigate the efficacy of SGB in terms of cerebral protection in patients undergoing CEA and to analyze its mechanism. METHODS: In this retrospective analysis, 120 patients who underwent CEA were enrolled and divided into study group (SG) (60 cases, general anesthesia and SGB) and control group (CG) (60 cases, general anesthesia). The differences in hemodynamic indexes, middle cerebral artery (MCA) hemodynamic indexes, and endocrine-related indexes between the two groups at the baseline, after induction of anesthesia (induction), and skin incision (incision) were compared. The differences in neurological function and pain level between two groups 1 day pre-operatively (pre-op 1), 1 day postoperatively (POD 1), 2 day postoperatively (POD 2), and 7 day postoperatively (POD 7) were also evaluated. Perioperative adverse events and intraoperative anesthetics dosage were compared between two groups. RESULTS: The systolic blood pressure, diastolic blood pressure, mean pulse pressure difference, and heart rate of SG at incision were lower than those of the CG (p < 0.05); Vs, Vd, and Vm of MCA were significantly higher in the SG than in CG at induction and incision (p < 0.05). Cortisol and aldosterone levels were lower and potassium and insulin levels were higher in the SG than in CG at induction and incision (p < 0.05); At pre-op 1, POD 1, POD 2, and POD 7, the VAS scores of patients in the SG were significantly lower than those in CG at POD 1, POD 2, and POD 7 (p < 0.05). The patients in SG showed decreased incidence of perioperative adverse events compared with the CG (p < 0.05); The consumption of anesthetics in the SG was lower than that in CG (p < 0.05). CONCLUSION: SGB in patients undergoing CEA treatment can improve perioperative cerebral blood supply and reduce the consumption of anesthetics and the incidence of perioperative adverse events, which is safe and feasible as a cerebral protection measure. Meanwhile, SGB may also help stabilize patients' perioperative hemodynamic indexes, but the result still needs to be supported by further large sample data.

One-dimensional coordinated polymers of tetraphenylethene pyridine and copper-iodide for fluorescence detection of nitroaromatic explosives.

The spatial arrangement of molecules plays a crucial role in determining the macroscopic properties of functional materials. Coordinated polymers (CPs) formed by self-assembly of organic isomeric ligands and metals offer unique performance characteristics. In this study, we present the investigation of a one-dimensional CP, named CIT-E, composed of tetraphenylethene pyridine derivative (TPE-2by-2-E) ligands and copper iodide. The resulting CP exhibits a one-dimensional bead chain structure with exceptional thermal and chemical stability. By leveraging the competitive absorption between CIT-E and the explosive analog 2,4-dinitroaniline, we achieve detection of the explosive through changes in the absorption intensity of the excitation light source and subsequent fluorescence response. The CP demonstrates high selectivity and anti-interference ability in detecting 2,4-dinitroaniline in aqueous solution, with a detection linear range of 0.1 to 300 µM and a detection limit of 0.05 µM, surpassing the national third-level emission standard. These findings highlight the potential of CP CIT-E as a promising material for the detection of explosive nitroaromatic compounds.

A comprehensive review of the metabolism of citrus flavonoids and their binding to bitter taste receptors.

Citrus is an important source of flavonoids in our daily diet. Citrus flavonoids have antioxidant, anticancer, anti-inflammatory, and cardiovascular disease prevention functions. Studies have shown that some pharmaceutical values of flavonoids may be related to their binding to bitter taste receptors, thus activating downstream signal transduction pathways; however, the underlying mechanism has not been systematically elucidated. In this paper, the biosynthesis pathway and the absorption and metabolism of citrus flavonoids were briefly reviewed, and the relationship between flavonoid structure and bitter taste intensity was investigated. In addition, the pharmacological effects of bitter flavonoids and the activation of bitter taste receptors in combating various diseases were discussed. This review provides an important basis for the targeted design of citrus flavonoid structures to make them more biologically active and more attractive as powerful drugs for the effective treatment of chronic diseases such as obesity, asthma, and neurological diseases.

Ligustrazine inhibits inflammatory response of human endometrial stromal cells through the STAT3/IGF2BP1/RELA axis.

CONTEXT: Endometriosis (EMs) is a gynecological disorder. Ligustrazine has been reported to exert an anti-inflammatory effect on EMs. However, the underlying mechanisms are not completely understood. OBJECTIVE: To investigate the effects of ligustrazine on the progression of EMs and the underlying regulatory mechanisms. MATERIALS AND METHODS: Human endometrial stromal cells (HESCs) were isolated from patients with EMs or control subjects. HESCs were treated with 25, 50, 100, or 200 µM ligustrazine for 1, 3, 6, or 12 h. Western blot and enzyme-linked immunosorbent assays were performed to determine the levels of proteins and inflammatory cytokines, respectively. The binding between STAT3 and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was assessed by chromatin immunoprecipitation and dual-luciferase reporter assays. The relationship between IGF2BP1 and RELA was assessed by RNA immunoprecipitation and RNA pull-down assay. RESULTS: Phosphorylated STAT3, IGF2BP1, RELA, TNF-α, IL-6, and IL-1ß were upregulated in EMs tissues compared with control tissues (by 1.79-, 2.55-, 1.58-, 3.01-, 2.55-, and 3.34-fold, respectively). Ligustrazine inhibited the expression of p-STAT3, IGF2BP1, RELA, IL-6, TNF-α, and IL-1ß. Overexpression of STAT3 promoted RELA-mediated inflammatory responses, while ligustrazine (100 µM) notably reversed this phenomenon. Ligustrazine also alleviated RELA-induced inflammation via downregulating IGF2BP1. STAT3 bound to the promoter of IGF2BP1, and IGF2BP1 bound to the RELA mRNA. DISCUSSION AND CONCLUSION: Ligustrazine inhibited inflammation in EMs via regulating the STAT3/IGF2BP1/RELA axis. These findings propose a new agent against EMs and support the development of ligustrazine-based treatment strategies for EMs.

PP2C1 fine-tunes melatonin biosynthesis and phytomelatonin receptor PMTR1 binding to melatonin in cassava.

Melatonin is an important molecule in both animals and plants, regulating circadian rhythms and stress responses. Therefore, the improvement of melatonin accumulation not only strengthens the function of melatonin but also improves stress resistance in crops. Although melatonin biosynthetic enzymes have been identified through reverse genetics previously, an investigation of melatonin level-related genes through forward genetics in plants has yet to be performed. In this study, a genome-wide association study using cassava natural population of 298 genetic resources identified melatonin accumulation 1 (MA1), which regulates the natural variation of melatonin levels in cassava. We found that MA1 encodes type 2C protein phosphatase 1 (PP2C1), which serves as a negative regulator of melatonin levels in cassava. MePP2C1 physically interacts with MeRAV1/2 and MeWRKY20 and dephosphorylates them at serine (S) 35 residue, S34 residue, and S176 residue, respectively, thereby hindering their transcriptional activation on downstream melatonin biosynthetic genes. Notably, MePP2C1 interacts with phytomelatonin receptor MePMTR1 and dephosphorylates it at S11 residue, repressing its binding to melatonin. In summary, this study demonstrates that MePP2C1 as MA1 plays dual roles in negatively regulating both melatonin accumulation and signaling, extending the understanding of the molecular mechanism underlying melatonin accumulation and signaling through forward genetics in plants.

Metal-Organic Framework with Near-Infrared Luminescence for "Switch-on" Determination of Kaempferol and Quercetin by the Antenna Effect.

The establishment of a reliable and sensitive method for the detection of flavonoids, such as kaempferol (Kae) and quercetin (Que), is important and challenging in food chemistry and pharmacology because numerous structural analogues may interfere with the detection. Until now, designing an efficient switch-on fluorescence sensing strategy for Kae and Que was still in the unachievable stage. In this work, a switch-on near-infrared (NIR) luminescence sensing assay for Kae and Que was fabricated based on a metal-organic framework (MOF) called IQBA-Yb for the first time. The fluorescence enhancing mechanism was that analytes served as additional "antenna" of Yb3+, leading to the efficient switch-on NIR emission under excitation at 467 nm. Meanwhile, the combination results of experiment and theoretical calculation revealed that there existed hydrogen bonds between Kae, Que, and the MOF skeleton, further promoting the energy transfer between the analyte and Yb3+ and facilitating fluorescence enhancement response. The developed probe possessed excellent sensing capability for Kae and Que, accompanied by a wide linear range (0.04-70, 0.06-90 µM), low detection limit (0.01, 0.06 µM), and short response time (20 min, 6 min), which was used to determine the Kae and Que contents in Green Lake and eatable Que samples with satisfactory results.

Engineering Aptamers with Selectively Enhanced Biostability in the Tumor Microenvironment.

Aptamers are emerging as promising molecular tools in cancer-targeted theranostics. Improving their in vivo stability has been a critical issue in promoting clinical translation, but such efforts could lead to more serious side effects resulting from prolonged retention in healthy organs. To address this problem, we developed an environment-responsive stabilization strategy for the selective enhancement of aptamer biostability in the tumor microenvironment (TME). Briefly, by means of the end extension of an ATP-responsive protection (ARP) module, the designed aptamer could be protected from nuclease degradation through the specific incorporation of ATP. Based on our in vivo results, this ARP-aptamer probe was effectively accumulated in tumors via aptamer-based molecular recognition. It showed selectively prolonged tumor retention time, but rapid digestion in healthy organs. Our strategy should provide a new paradigm for the development of organ-specific nucleic acid-based imaging and therapeutic agents.

DNA-Based Dynamic Mimicry of Membrane Proteins for Programming Adaptive Cellular Interactions.

Cells sense and respond to the external environment, mainly through proteins presented on the membrane where their expression and conformation are dynamically regulated via intracellular programs. Here, we engineer a cell-surface nanoarchitecture that realizes molecular-recognition-initiated DNA assembly to mimic the dynamic behavior of membrane proteins, enabling the manipulation of cellular interaction in response to environmental changes. Our results show that this membrane-anchored DNA nanoarchitecture can be specifically activated by cell-responsive signals to external stimulation. Accordingly, multiple functional modules can be assembled onto the membrane to equip the cell with cell-type-specific binding and killing. This system is expected to offer a new paradigm for engineering therapeutic cells with customized sensing/response pathways.

Morphology-Dependent Peroxidase Mimicking Enzyme Activity of Copper Metal-Organic Polyhedra Assemblies.

The morphology of nanomaterials (geometric shape and dimension) play a significant role in its various physical and chemical properties. Thus, it is essential to link morphology with performance in specific applications. For this purpose, the morphology of copper metal-organic polyhedra (Cu-MOP) can be modulated through distinct assembly process, which facilitates the exploration of the relationship between morphology and catalytic performance. In this work, the assemblies of Cu-MOP with three different morphologies (nanorods, nanofibers and nanosheets) were facilely prepared by the variation of solvent mixture of N, N-dimethylformamide (DMF) and methanol, revealed the important role of the interaction between the surface group and the solvent on the morphology of these assemblies. Cu-MOP nanofibers exhibited the highest mimetic peroxidase enzyme activity over the Cu-MOP nanosheets and nanorods, which have been utilized in the detection of glucose. Cu-MOPs assemblies with tunable morphology accompanied with adjustable mimic peroxidase activity, had great potential applications in the field of bioanalytical chemistry and biomedicals.

Reversible Photochromic Coordination Polymer by Phototriggered Subtle Molecular Conformation Variations.

Photochromic materials are constructed with molecules accompanied by structural change after triggering by light, which are of great importance and necessity for various applications. However, because of space-confinement effects, molecule stacking of these photoresponsive chromophores within coordination polymers (CPs) always results in an efficiency decrement and a response delay, and this phenomenon will lead to a poor photochromic property. Herein, a CP (named CIT-E) with a 3-fold-interpenetrating network structure, which was prepared with (Z)-1,2-diphenyl-1,2-bis[4-(pyridin-3-ylmethoxy)phenyl]ethene (1Z) and a CuI cluster, showed fast reversible photochromic behavior. Under UV-light illumination, the color of CIT-Z changed from pale yellow to reddish brown. With the illumination of green light, the polymer could return to its initial color within 10 s. To reveal the mechanism of reversible photochromic behavior of CIT-Z, single-crystal structures of each color state were fully studied, and other scientific study methods were also used, such as time-dependent density functional theory calculation and control experiments. It was found that, with light illumination, this behavior of CIT-Z was the result of a ligand-to-metal charge-transfer process, and this process was triggered by subtle molecular conformation variation of tetraphenylethylene. It should be noted that CIT-Z has high thermal and chemical stability, which are excellent advantages as smart photoresponsive materials. As a proof of concept, a uniform thin film with such a fascinating photochromic property allows applications in invisible anticounterfeiting and dynamic optical data storage. Overall, the present study opens up a new avenue toward reversible photochromic materials.

Accurate assessment of parabens exposure in healthy Chinese female adults: Findings from a multi-pathway exposure assessment coupled with intervention study.

Exposure of humans to parabens is widespread and urinary parabens are widely used as exposure biomarkers. However, are the levels of these chemicals suitable to assess exposure to parabens? We conducted an intervention study by controlling the use of personal care products (PCPs) to explore the exposure of parabens. Ten female participants were recruited who were treated with different types of PCPs during the 18-day study period. The concentrations of parabens and their metabolites in matrices of different exposure pathways (dust, drinking water and dietary food) and urine samples were determined. We demonstrated that PCPs were the major sources of parabens, accounting for >99% of total exposure. The metabolites were nonspecific to individual parabens and could not be used as exposure biomarkers. Urinary paraben concentrations were positively correlated with external exposure levels. However, poor reproducibility was observed, with intraclass correlation coefficients (ICC) ranging from 0.125 to 0.295 in unadjusted urinary concentrations. Creatinine-adjusting could not significantly improve the ICC values in random spot samples. After adjusting for both creatinine and kinetic models, the ICC values ranged from 0.695 to 0.886, indicating a good reproducibility. So, toxicokinetic parameters may be taken into consideration for precise monitoring of exposures for the non-persistent pollutants.

In Vivo Monocyte/Macrophage-Hitchhiked Intratumoral Accumulation of Nanomedicines for Enhanced Tumor Therapy.

The inner region of solid tumors is found to be high-pressure, hypoxic, and immunosuppressive, providing a breeding ground for tumor aggressiveness and metastasis. While intratumoral accumulation of nanomedicines combined with immunomodulation would significantly enhance therapeutic efficacy, such potential is challenged by the compressed environment and distinct heterogeneity of the tumor bulk. By using an apoptotic body (AB) as the carrier, we develop an effective and universal intratumoral nanomedicine delivery system for the long-lasting remission of tumors. Our results show that the AB-encapsulated nanomedicine (using CpG immunoadjuvant-modified gold-silver nanorods as a model), after intravenous injection, can be specifically phagocytosed by inflammatory Ly-6C+ monocytes, which then actively infiltrate the tumor center via their natural tumor-homing tendency. With the integration of AB-facilitated intratumoral accumulation, the nanorod-based photothermal effect, and CpG-promoted immunostimulation, this cell-mediated delivery system can not only efficiently ablate primary tumors but also elicit a potent immunity to prevent tumors from metastasizing and recurring.