High-Resolution and Dynamic Visualization of Intracellular Redox Potential Using a Metal-Organic Framework-Functionalized Nanopotentiometer.

Redox potential plays a key role in regulating intracellular signaling pathways, with its quantitative analysis in individual cells benefiting our understanding of the underlying mechanism in the pathophysiological events. Here, a metal organic framework (MOF)-functionalized SERS nanopotentiometer has been developed for the dynamic monitoring of intracellular redox potential. The approach is based on the encapsulation of zirconium-based MOF (Uio-66-F4) on a surface of gold-silver nanorods (Au-Ag NRs) that is modified with the newly synthesized redox-sensitive probe ortho-mercaptohydroquinone (HQ). Thanks to size exclusion of MOF as the chemical protector, the nanopotentiometer can be adapted to long-term use and possess high anti-interference ability toward nonredox species. Combining the superior fingerprint identification of SERS with the electrochemical activity of the quinone/hydroquinone, the nanopotentiometer shows a reversible redox responsivity and can quantify redox potential with a relatively wide range of -250-100 mV. Furthermore, the nanopotentiometer allows for dynamic visualization of intracellular redox potential changes induced by drugs' stimulation in a high-resolution manner. The developed approach would be promising for offering new insights into the correlation between redox potential and tumor proliferation-involved processes such as oxidative stress and hypoxia.

The Arabidopsis RTH plays an important role in regulation of iron (Fe) absorption and transport.

KEY MESSAGE: RTH may activate Fe assimilation related genes to promote Fe absorption, transport and accumulation in Arabidopsis. Iron (Fe) is an important nutrient element. The Fe absorption and transport in plants are well investigated over the past decade. Our previous work indicated that RTE1-HOMOLOG (RTH), the homologous gene of reversion-to-ethylene sensitivity 1 (RTE1), plays a role in ethylene signaling pathway. However, its function in Fe absorption and transport is largely unknown. In the present study, we found that RTH was expressed in absorptive tissue and conducting tissue, including root hairs, root vascular bundle, and leaf veins. Under high Fe concentration, the seedling growth of rth-1 mutant was better, while the RTH overexpression lines were retarded compared to the wild type (Col-0). When treated with EDTA-Fe3+ (400 µM), the chlorophyll content and ion leakage rate were higher and lower in rth-1 than those of Col-0, respectively. By contrast, the chlorophyll contents and ion leakage rates of RTH overexpression lines were decreased and hastened compared with Col-0, respectively. Fe measurement indicated that the Fe contents of rth-1 were lower than those of Col-0, whereas those of RTH overexpression lines were comparably higher. Gene expression analysis revealed that Fe absorption and transport genes AHA2, IRT1, FIT, FPN1, and YSL1 decreased in rth-1 but increased in RTH overexpression lines compared with Col-0. Additionally, Y2H (yeast two-hybrid) and BiFC (bimolecular fluorescence complementation) assays showed that RTH can physically interact with hemoglobin 1 (HB1) and HB2. All these findings suggest that RTH may play an important role in regulation of Fe absorption, transport, and accumulation in Arabidopsis.

Cascade reaction triggered colorimetric array for identification of organophosphorus pesticides congeners.

A modern agriculture uses alternative pest control methods to boost productivity, leading to an accumulation of organophosphorus (OPPs) congeners. This necessitates an intuitive and quick way to identify OPPs congeners. A colorimetric sensor for detecting OPPs congeners using a double-enzyme cascade reaction has been successfully designed and constructed in this study. The OPPs regulate the color changes induced by manganese dioxide nanoflowers (MnO2 NFs) and specific alkaline phosphatases (ALP) during the etching of gold nanopyramids (Au NBPs). The ascorbic acid (AA) produced by ALP hydrolysis inhibits Au NBPs etching by MnO2 NFs oxidized 3, 3', 5, 5'-tetramethylbenzidine (TMB). By inhibiting ALP catalytic activity, OPPs prevent AA formation. In this process, Au NBPs will undergo further etching, resulting in various colors so they can be analyzed semi-quantitatively with the naked eye. It has been found that different types of OPPs inhibit enzymes differently and therefore result in varying degrees of etching of Au NBPs. Principal Component Analysis (PCA) is performed by smart devices that convert R, G, and B signals into digital signals. This colorimetric array tests various foods (tea, apple, and cabbage). Colorimetric visualization sensors combined with data analysis will be used in real-life product development.

3D hotspot engineering and analytes strategy enabled ultrasensitive SERS platform for biosensing of depression biomarker.

Nowadays, the diagnose of depression mainly relies on clinical examination while impossible to accurately evaluate the occurrence of depression. Chemical approaches are captivating to analyze stress biomarkers for feedbacking body's endocrine response to stress stimuli. However, it remains challenging in exploring accurate, reliable and sensitive approaches. Herein, we rationally design a newly SERS platform with integrated hotspots engineering and analyte strategy to achieve highly sensitive analysis for estrogen, a typical depression biomarker in adolescent female. On the one hand, the 3D micro/nano plasmonic substrate containing Au-Ag Alloy Nanourchins (AAA-NUs) and arrays-based monolayer films of Au nanoparticles (Au NSs) was constructed to achieve high density and availability of hotspots. On the other hand, the analyte strategy was designed via rapid azotizing reaction to further enhance the scattering cross-section of estrogen in the form of azido compounds. With the synergism of them, the proposed SERS platform displayed high sensitivity for estrogen with a limit of detection down to 10-11 mg/mL. More importantly, the blood estrogen levels of depressed patients were evaluated via the proposed SERS platform and presented high consistence with clinical diagnostic results. This integrated SERS platform paves the way for universal and ultrasensitive biosensing and possess great potential for applying in multi-target detection and disease prediction.

Plasmonic Multi-Layered Built-in Hotspots Nanogaps for Effectively Activating Analytes.

Multi-layered plasmonic nanostructures are able to highly promote the near-field confinement and effectively activate analytes, which are of predominate significance but are extremely challenging. Herein, the semi-open Au core@carved AuAg multi-shell superstructure nanoparticles (multi-Au@Ag-Au NPs, multi = mono, bi, tri, tetra, and penta) are reported with a high designability on electromagnetic field and capability of effectively capturing analytes. By controlling synthetic parameters such as the number of galvanic exchange and Ag growth, multi-Au@Ag-Au NPs are successfully obtained, with tunable layer numbers and asymmetric nanoholes. Due to collective plasmon oscillations of multi-layered built-in nanogaps, the electromagnetic field strength of a single penta-Au@Ag-Au entity reach 48841. More importantly, the penta-Au@Ag-Au NPs show a remarkable light-harvesting capability, which is adaptive to different Raman lasers, supporting high-diversity detection. Additionally, the structural specificity allows analytes to be sufficiently captured into interior hotspots, and further achieve highly sensitive detection with limit of detection down to 3.22 × 10-12  M. This study not only provides an effective pathway for integrating abundant hotspots and activating target molecules in single plasmonic superstructure, but stimulates advancements in SERS substrates for various applications.

Kinetically matched C-N coupling toward efficient urea electrosynthesis enabled on copper single-atom alloy.

Chemical C-N coupling from CO2 and NO3-, driven by renewable electricity, toward urea synthesis is an appealing alternative for Bosch-Meiser urea production. However, the unmatched kinetics in CO2 and NO3- reduction reactions and the complexity of C- and N-species involved in the co-reduction render the challenge of C-N coupling, leading to the low urea yield rate and Faradaic efficiency. Here, we report a single-atom copper-alloyed Pd catalyst (Pd4Cu1) that can achieve highly efficient C-N coupling toward urea electrosynthesis. The reduction kinetics of CO2 and NO3- is regulated and matched by steering Cu doping level and Pd4Cu1/FeNi(OH)2 interface. Charge-polarized Pdδ--Cuδ+ dual-sites stabilize the key *CO and *NH2 intermediates to promote C-N coupling. The synthesized Pd4Cu1-FeNi(OH)2 composite catalyst achieves a urea yield rate of 436.9 mmol gcat.-1 h-1 and Faradaic efficiency of 66.4%, as well as a long cycling stability of 1000 h. In-situ spectroscopic results and theoretical calculation reveal that atomically dispersed Cu in Pd lattice promotes the deep reduction of NO3- to *NH2, and the Pd-Cu dual-sites lower the energy barrier of the pivotal C-N coupling between *NH2 and *CO.

Programming actuation onset of a liquid crystalline elastomer via isomerization of network topology.

Tuning actuation temperatures of liquid crystalline elastomers (LCEs) achieves control of their actuation onsets, which is generally accomplished in the synthesis step and cannot be altered afterward. Multiple actuation onsets in one LCE can be encoded if the post-synthesis regulation of actuation temperature can be spatiotemporally achieved. This would allow realizing a logical time-evolution of actuation, desired for future soft robots. Nevertheless, this task is challenging given the additional need to ensure mesogen alignment required for actuation. We achieved this goal with a topology isomerizable network (TIN) of LCE containing aromatic and aliphatic esters in the mesogenic and amorphous phases, respectively. These two ester bonds can be distinctly activated for transesterification. The homolytic bond exchange between aliphatic esters allows mechanically induced mesogen alignment without affecting the mesogenic phase. Most importantly, the heterolytic exchange between aromatic and aliphatic esters changes the actuation temperature under different conditions. Spatial control of the two mechanisms via a photo-latent catalyst unleashes the freedom in regulating actuation temperature distribution, yielding unusual controllability in actuation geometries and logical sequence. Our principle is generally applicable to common LCEs containing both aromatic and aliphatic esters.

Distinguishable Colorimetric Biosensor for Diagnosis of Prostate Cancer Bone Metastases.

Castration-resistant prostate cancer (PCa) causes severe bone metastasis (BM), which significantly increases mortality in men with PCa. Imaging tests and radiometric scanning require long analysis times, expensive equipment, specialized personnel, and a slow turnaround. New visualization technologies are expected to solve the above problems. Nonetheless, existing visualization techniques barely meet the urgency for precise diagnosis because the human eyes cannot recognize and capture even slight variations in visual information. By using dye differentiated superposition enhancement colorimetric biosensors, an effective method to diagnose prostate cancer bone metastases (PCa-BM) with excellent accuracy for naked-eye quantitative detection of alkaline phosphatase (ALP) is developed. The biomarker ALP specific hydrolytic product ascorbic acid can be detected by rhodamine derivatives (Rd) as gold nanobipyramids (Au NBPs) are deposited and grown. Color-recombining enhancement effects between Rd and Au NBPs significantly improved abundance. The 150 U L-1 threshold between normal and abnormal can be identified by color. And with color enhancement effect and double signal response, the ALP index is visually measured to diagnose PCa-BM and provide handy treatment recommendations. Additionally, the proposed colorimetric sensing strategy can be used to diagnose other diseases.

Nanohole-Array Induced Metallic Molybdenum Selenide Nanozyme for Photoenhanced Tumor-Specific Therapy.

Deficient catalytic sensitivity to the tumor microenvironment is a major obstacle to nanozyme-mediated tumor therapy. Electron transfer is the intrinsic essence for a nanozyme-catalyzed redox reaction. Here, we developed a nanohole-array-induced metallic molybdenum selenide (n-MoSe2) that is enriched with Se vacancies and can serve as an electronic transfer station for cycling electrons between H2O2 decomposition and glutathione (GSH) depletion. In a MoSe2 nanohole array, the metallic phase reaches up to 84.5%, which has been experimentally and theoretically demonstrated to exhibit ultrasensitive H2O2 responses and enhanced peroxidase (POD)-like activities for H2O2 thermodynamic heterolysis. More intriguingly, plenty of delocalized electrons appear due to phase- and vacancy-facilitated band structure reconstruction. Combined with the limited characteristic sizes of nanoholes, the surface plasmon resonance effect can be excited, leading to the broad absorption spectrum spanning of n-MoSe2 from the visible to near-infrared region (NIR) for photothermal conversion. Under NIR laser irradiation, metallic MoSe2 is able to induce out-of-balance redox and metabolism homeostasis in the tumor region, thus significantly improving therapeutic effects. This study that takes advantage of phase and defect engineering offers inspiring insights into the development of high-efficiency photothermal nanozymes.

Logic gate-driven dual-index balanced visualization strategy for tumor metastasis diagnosis.

Exfoliated tumor cells are integral to malignant tumors diagnosis. The process of clinical cytology of exfoliation involves several complex steps that require at least two days of preparation. Here, we develop a balanced-etching visual kit based on concentration differences of Glutathione/Glucose (GSH/Glu) to distinguish normal from exfoliated tumor cells rapidly and accurately. The balanced-etching visualization kit can be used to obtain color cards and screen exfoliated tumor cells initially (within 10 min). Furthermore, by utilizing logic gates and machine learning algorithms for RGB extraction of the color card obtained from the kit, accurate screening of exfoliated tumor cells is achieved. Finally, a series of clinical tumor samples, such as urine, pleural fluids, ascites, and gastric fluids, have been validated. With effective experimental methods, accurate disease information, and appropriate therapeutic programs, the novel diagnostic strategy is expected to promote precision medicine.

Highly-oxidizing Au@MnO2-X nanozymes mediated homogeneous electrochemical detection of organophosphorus independent of dissolved oxygen.

Traditional oxidase-like (OXD) nanozymes rely primarily on O2-mediated superoxide anion (O2·-) process for catalytic oxidation and organophosphorus (Ops) detection. While during the actual detection process, the concentration of O2 is inconstant that can be easily changed with the external environment, distorting detection results. Herein, highly-oxidizing Au@MnO2-X nanozymes with core-shell nanostructure are designed which trigger substantial electron transfer from inner Au core to outer ultrathin MnO2-X layer. According to experimental and theoretical calculations, the core-shell nanostructure and ultrathin MnO2-X of Au@MnO2-X result in the large surface defects, high oxygen vacancies and MnIII ratios. The specially structured Au@MnO2-X nanozymes are therefore highly-oxidizing and the catalytic oxidation can be completed merely through electrons transferring instead of the O2-mediated O2·- process. Based on this, an oxygen independent and ultrasensitive nanozyme-based sensor is established using homogeneous electrochemistry (HEC), its Ops is detected at a LOD of 0.039 ng mL-1. Combined with the UV-vis spectrum of 3,3',5,5'-tetramethylbenzidine (TMB), the linear discriminant analysis of five Ops i.e., Ethion, Omethoate, Diazinon, Chlorpyrifos methyl and Dipterex has achieved superior discrimination results. Therefore, HEC based on strong oxidizing nanozymes provide a new avenue for the development of high-performance electrochemical sensors and demonstrate potential applicability to pesticide residue determination in real samples.

Dual enzyme induced colorimetric sensor for simultaneous identifying multiple pathogens.

Rapid and accurate identification of foodborne pathogens improves public health. Currently employed methods are time-consuming, sensitive to environmental factors, and complex. This study develops a colorimetric sensor for detecting multiple bacteria with one probe using double-enzyme-induced colorimetry. Based on alkaline phosphatase (ALP) in bacteria decomposes L-ascorbic acid 2-magnesium phosphate salt hydrate into ascorbic acid (AA). Manganese dioxide flowers (MnO2 NFs) can oxidize TMB to etch gold nanorods (Au NRs), which can be inhibited by AA reduction to produce rich colors. Bacteria with varying ALP levels can be identified based on color changes and plasmon resonance wavelength signals produced from Au NRs. Furthermore, the conversion of RGB signals to digital signals and the use of linear discriminant analysis (LDA) allowed 99.57% accuracy in identifying multiple bacteria. It can simultaneously identify five foodborne pathogens across diverse environments (shrimp, meat, milk, etc.). This method may be useful for the rapid and simple identification of foodborne illnesses.

Ratiometric near-infrared upconversion fluorescence sensor for selectively detecting and imaging of Al3.

Near-infrared (NIR) fluorescent probes provide extremely sensitive Al3+ detection for human health purposes. This research develops novel Al3+ response molecules (HCMPA) and NIR upconversion fluorescent nanocarriers (UCNPs), which respond to Al3+ through ratio NIR fluorescence. UCNPs improve photobleaching and visible light lack in specific HCMPA probes. Additionally, UCNPs are capable of ratio response, which will further enhance signal accuracy. The NIR ratiometric fluorescence sensing system has been successfully used to detect Al3+ within the range 0.1-1000 nM with an accuracy limit of 0.06 nM. Alternatively, a NIR ratiometric fluorescence sensing system integrated with a specific molecule can image Al3+ within cells. This study demonstrates that a NIR fluorescent probe is an effective and highly stable method of measuring Al3+ in cells.

Naturally sourced hydrogels: emerging fundamental materials for next-generation healthcare sensing.

The flourishing development of flexible healthcare sensing systems is inseparable from the fundamental materials with application-oriented mechanical and electrical properties. Thanks to continuous inspiration from our Mother Nature, flexible hydrogels originating from natural biomass are attracting growing attention for their structural and functional designs owing to their unique chemical, physical and biological properties. These highly efficient architectural and functional designs enable them to be the most promising candidates for flexible electronic sensing devices. This comprehensive review focuses on the recent advances in naturally sourced hydrogels for constructing multi-functional flexible sensors and healthcare applications thereof. We first briefly introduce representative natural polymers, including polysaccharides, proteins, and polypeptides, and summarize their unique physicochemical properties. The design principles and fabrication strategies for hydrogel sensors based on these representative natural polymers are outlined after the fundamental material properties required in healthcare sensing applications are presented. We then highlight the various fabrication techniques of natural hydrogels for sensing devices, and illustrate the representative examples of wearable or implantable bioelectronics for pressure, strain, temperature, or biomarker sensing in the field of healthcare systems. Finally, concluding remarks on challenges and prospects in the development of natural hydrogel-based flexible sensors are provided. We hope that this review will provide valuable information for the development of next-generation bioelectronics and build a bridge between the natural hydrogels as fundamental matter and multi-functional healthcare sensing as an applied target to accelerate new material design in the near future.

TiO2 compact layer induced charge transfer enhancement in a three-dimensional TiO2-Ag array SERS substrate for quantitative and multiplex analysis.

A highly sensitive and uniform surface-enhanced Raman scattering (SERS) substrate is the guarantee for reliable quantitative analysis. Herein, a three-dimensional TiO2-Ag SERS substrate was prepared by growing a TiO2 nanorods (NRs) array on a TiO2 compact layer (c-TiO2), followed by modification with Ag nanoparticles (AgNPs). The synergy between the c-TiO2, semiconductor TiO2 NRs and the plasmonic AgNPs collaboratively endowed it with high sensitivity, in which c-TiO2 effectively blocked the recombination of electrons and holes, and the charge transfer enhancement contributed 10-fold improvement over that without the c-TiO2 substrate. Besides the high sensitivity, the TiO2-Ag hybrid array SERS substrate also showed quantitative and multi-component detecting capability. The limit of detection (LOD) for crystal violet (CV) was determined to be 10-9 M even with a portable Raman instrument. The TiO2-Ag composite structure was extended to detect organic pesticides (thiram, triazophos and fonofos), and the LODs for thiram, triazophos and fonofos were measured to be 10-7 M, 10-7 M and 10-6 M, respectively. In addition, the realistic simulation detecting pesticide residues for a real sample of dendrobium was demonstrated. The sensitive, quantitative and multiplex analysis of the TiO2-Ag hybrid array substrate indicated its great potential in the rapid detection of pesticide residues in real samples.

Multienzyme-Mimicking Au@Cu2O with Complete Antioxidant Capacity for Reactive Oxygen Species Scavenging.

Most enzyme catalysts are unable to achieve effective oxidation resistance because of the monotonous mimicking function or production of secondary reactive oxygen species (ROS). Herein, the Au@Cu2O heterostructure with multienzyme-like activities is deigned, which has significantly improved antioxidant capacity compared with pure Cu2O for the scavenging of highly cell-damaging secondary ROS, i.e.,·OH. Experiments and theoretical calculations show that the heterostructure exhibits a built-in electric field and lattice mismatch at the metal-semiconductor interface, which facilitate to generate abundant oxygen vacancies, redox couples, and surface electron deficiency. On the one hand, the presence of rich oxygen vacancies and redox couple can enhance the adsorption and activation of oxygen-containing ROS (including O2·- and H2O2). On the other hand, the electron transfer between the electron-deficient Au@Cu2O surface and electron donor would promote peroxide-like activity and avoid producing ·OH. Importantly, endogenous ·OH could be eliminated in both acidic and neutral conditions, which is no longer limited by the volatile physiological environment. Therefore, Au@Cu2O can simulate superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione peroxidase (GPx) to form a complete antioxidant system. The deigned nanoenzyme is explored in the real sample world such as A549 cells and zebrafish. This work provides theoretical and practical strategies for the construction of a complete antioxidant enzyme system.

DSCA-PSPNet: Dynamic spatial-channel attention pyramid scene parsing network for sugarcane field segmentation in satellite imagery.

Sugarcane plays a vital role in many global economies, and its efficient cultivation is critical for sustainable development. A central challenge in sugarcane yield prediction and cultivation management is the precise segmentation of sugarcane fields from satellite imagery. This task is complicated by numerous factors, including varying environmental conditions, scale variability, and spectral similarities between crops and non-crop elements. To address these segmentation challenges, we introduce DSCA-PSPNet, a novel deep learning model with a unique architecture that combines a modified ResNet34 backbone, the Pyramid Scene Parsing Network (PSPNet), and newly proposed Dynamic Squeeze-and-Excitation Context (D-scSE) blocks. Our model effectively adapts to discern the importance of both spatial and channel-wise information, providing superior feature representation for sugarcane fields. We have also created a comprehensive high-resolution satellite imagery dataset from Guangxi's Fusui County, captured on December 17, 2017, which encompasses a broad spectrum of sugarcane field characteristics and environmental conditions. In comparative studies, DSCA-PSPNet outperforms other state-of-the-art models, achieving an Intersection over Union (IoU) of 87.58%, an accuracy of 92.34%, a precision of 93.80%, a recall of 93.21%, and an F1-Score of 92.38%. Application tests on an RTX 3090 GPU, with input image resolutions of 512 × 512, yielded a prediction time of 4.57ms, a parameter size of 22.57MB, GFLOPs of 11.41, and a memory size of 84.47MB. An ablation study emphasized the vital role of the D-scSE module in enhancing DSCA-PSPNet's performance. Our contributions in dataset generation and model development open new avenues for tackling the complexities of sugarcane field segmentation, thus contributing to advances in precision agriculture. The source code and dataset will be available on the GitHub repository https://github.com/JulioYuan/DSCA-PSPNet/tree/main.

Ultrasensitive Sandwich-Type SERS-Biosensor-Based Dual Plasmonic Superstructure for Detection of Tacrolimus in Patients.

Tacrolimus (FK506) is widely used in the prevention of organ transplant rejection and the treatment of autoimmune diseases, but it is difficult to detect within the low and narrow concentration range in practical clinical fields. A magnetic plasmonic superstructure-targets-plasmonic superstructure-based sandwich-type SERS biosensor is presented here to ultrasensitively detect FK506 in the blood of organ transplant patients. The spiky Fe3O4@SiO2@Ag flower magnetic superstructure and hollow Ag@Au superstructure enhanced the SERS signals by providing rich sharp tips, cavities, and abundant hot spot gaps. And the magnetic feature makes it easy to concentrate and separate the biological target. Using the designed sandwich-type SERS biosensor, FK506 could be detected within a range of 0.5-20 ng/mL with a detection limit of 0.33 ng/mL. All results indicated that the sandwich-type SERS biosensor has good stability, sensitivity, and anti-interference properties. It is noteworthy that this allowed us to successfully analyze FK506 in the blood of transplant patients, which is in strong agreement with the clinical results. Consequently, the attractive sandwich-type SERS biosensor can be used for the detection of FK506 in real samples, which is promising for clinical diagnosis.

Tyrosine kinase receptor RON activates MAPK/RSK/CREB signal pathway to enhance CXCR4 expression and promote cell migration and invasion in bladder cancer.

Bladder cancer (BC) is one of the most lethal malignancies worldwide. The poor survival may be due to a high proportion of tumor metastasis. RON and CXCR4 are the key regulators of cell motility in BC, while the relationship between RON and CXCR4 remains elusive. In the present study, immunohistochemistry analysis of BC and adjacent normal tissues found that higher RON expression was positively correlated with CXCR4 expression. Inhibiting and replenishing RON level were used to regulate CXCR4 expression, observing the effects on migration and invasion of BC cells. Overexpression of RON reversed the inhibited cell migration and invasion following siCXCR4 treatment. Conversely, overexpression of CXCR4 restored the inhibition of cell migration and invasion caused by shRON. The activation of RON-MAPK/RSK/CREB pathway was demonstrated in BC cells under MSP treatment. Dual luciferase and CHIP assay showed that p-CREB targeted CXCR4 by binding to its CRE sequence. RON knockdown suppressed BC tumor growth in xenograft mouse tumors, accompanied by reduced expression of CXCR4. In conclusion, our data adds evidence that RON, a membrane tyrosine kinase receptor, promotes BC migration and invasion not only by itself, but also by activating MAPK/RSK/CREB signaling pathway to enhance CXCR4 expression.

Etched-spiky Au@Ag plasmonic-superstructure monolayer films for triple amplification of surface-enhanced Raman scattering signals.

Generally, a high quality surface-enhanced Raman spectroscopy (SERS) substrate often requires a highly-tailorable electromagnetic (EM) field generated at nanoparticle (NP) surfaces by the regulation of the morphologies, components and roughness of NPs. However, most recent universal approaches are restricted to single components, and integrating these key factors into one system to achieve the theoretically maximum signal amplification is still challenging. Herein, we design a triple SERS signal amplification platform by the coordination of spiky Au NPs with rich-tip nanostructures, controllable silver nanoshell, as well as tailorable surface roughness into one nano-system. As a result, the theoretical electromagnetic field of the interfacial self-assembled 2D substrate can be improved by nearly 5 orders of magnitude, and the ideal tracing capability for the model SERS molecule can be achieved at levels of 5 × 10-11 M. Finally, diverse analytes in pesticide residues, environmental pollutants as well as medically diagnose down to 10-11 M and can be fingerprinted by the proposed SERS nano-platform. Our integrated triple amplification platform not only provides an effective SERS sensing strategy, but also makes it possible to simultaneously achieve high sensitivity, stability as well as universality into one plasmonic-based SERS sensing system.