ABSTRACT
Constructing versatile metal nanoclusters (NCs) assemblies through noncovalent weak interactions between inter-ligands is a long-standing challenge in interfacial chemistry, while compelling interfacial hydrogen-bond-driven metal NCs assemblies remain unexplored so far. Here, the study reports an amination-ligand o-phenylenediamine-coordinated copper NCs (CuNCs), demonstrating the impact of interfacial hydrogen-bonds (IHBs) motifs on the luminescent behaviors of metal NCs as the alteration of protic solvent. Experimental results supported by theoretical calculation unveil that the flexibility of interfacial ligand and the distance of cuprophilic CuI···CuI interaction between intra-/inter-NCs can be tailored by manipulating the cooperation between the diverse IHBs motifs reconstruction, therewith the IHBs-modulated fundamental structure-property relationships are established. Importantly, by utilizing the IHBs-mediated optical polychromatism of aminated CuNCs, portable visualization of humidity sensing test-strips with fast response is successfully manufactured. This work not only provides further insights into exploring the interfacial chemistry of NCs based on inter-ligands hydrogen-bond interactions, but also offers a new opportunity to expand the practical application for optical sensing of metal NCs.
ABSTRACT
Currently, the nanofluidic synapse can only perform basic neuromorphic pulse patterns. One immediate problem that needs to be addressed to further its capability of brain-like computing is the realization of a nanofluidic spiking device. Here, we report the use of a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate membrane to achieve bionic ionic current-induced spiking. In addition to the simulation of various electrical pulse patterns, our synapse could produce transmembrane ionic current-induced spiking, which is highly analogous to biological action potentials with similar phases and excitability. Moreover, the spiking properties could be modulated by ions and neurochemicals. We expect that this work could contribute to biomimetic spiking computing in solution.
Subject(s)
Action Potentials , Polystyrenes , Synapses , Action Potentials/physiology , Synapses/physiology , Polystyrenes/chemistry , Nanotechnology/methods , Nanotechnology/instrumentationABSTRACT
The dynamics of ion transport at the interface is the critical factor for determining the performance of an electrochemical energy storage device. While practical applications are realized in concentrated electrolytes and nanopores, there is a limited understanding of their ion dynamic features. Herein, we studied the interfacial ion dynamics in room-temperature ionic liquids by transient single-particle imaging with microsecond-scale resolution. We observed slowed-down dynamics at lower potential while acceleration was observed at higher potential. Combined with simulation, we found that the microstructure evolution of the electric double layer (EDL) results in potential-dependent kinetics. Then, we established a correspondence between the ion dynamics and interfacial ion composition. Besides, the ordered ion orientation within EDL is also an essential factor for accelerating interfacial ion transport. These results inspire us with a new possibility to optimize electrochemical energy storage through the good control of the rational design of the interfacial ion structures.
ABSTRACT
OBJECTIVE: To investigate the effects of electroacupuncture combined with paliperidone palmitate long-acting injection (PP-LAI) on withdrawal symptoms and neurotransmitters in methamphetamine (MA) addicts. MATERIALS AND METHODS: A total of 109 methamphetamine addicts, who were treated in the hospital from October 2021 to October 2022, were selected. According to the random number table, the patients were divided into the study group (n=54) and the control group (n=55), in which the control group was treated with PP-LAI and the study group was treated with electroacupuncture on the basis of the control group; the methamphetamine withdrawal symptom score scale was used to assess the therapeutic effect before treatment and within 12 months after treatment; the changes of brain neurotransmitters dopamine, γ-aminobutyric acid, serotonin, acetylcholine values were compared between the two groups. RESULTS: 1) There was no statistical difference in MA withdrawal symptom scores between the two groups before treatment (p>0.05); 2) MA withdrawal symptom scores have a statistically significant difference between the study group and the control group after 3 and 6 months of treatment; 3) dopamine levels in the study group were significantly higher than those in the control group after 6 months of completion of treatment, and γ-aminobutyric acid values and 5- serotonin values in the study group were significantly lower than those in the control group (p<0.05). CONCLUSIONS: Electroacupuncture combined with PP-LAI can partially improve the withdrawal symptoms and anxiety of methamphetamine addicts. This is a potential treatment for preventing relapse of withdrawal symptoms.
Subject(s)
Amphetamine-Related Disorders , Delayed-Action Preparations , Electroacupuncture , Methamphetamine , Neurotransmitter Agents , Paliperidone Palmitate , Substance Withdrawal Syndrome , Humans , Paliperidone Palmitate/administration & dosage , Paliperidone Palmitate/therapeutic use , Methamphetamine/adverse effects , Methamphetamine/administration & dosage , Male , Adult , Amphetamine-Related Disorders/therapy , Female , Neurotransmitter Agents/metabolism , Combined Modality Therapy , Dopamine/metabolism , Serotonin/metabolism , gamma-Aminobutyric Acid , Middle Aged , Treatment Outcome , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effectsABSTRACT
Myxoid liposarcoma (MLPS) of the parotid gland is very rare, and only a few cases have been reported worldwide. It can be difficult to diagnose this disease when there is only a single lesion in the patient's body. A 56-year-old man was diagnosed with an MLPS in the left calf and was treated with wide resection. Two months after the surgery, a painless mass appeared in the man's left parotid gland area. Both fine-needle aspiration biopsy before surgery and intraoperative frozen sections suggested that the tumor was likely to be a pleomorphic adenoma. Both parotid ultrasound and CT indicated the same result. However, this mass was confirmed to be metastasis of MLPS through immunohistochemistry and multicolor fluorescence in situ hybridization. The authors report a case in which an MLPS metastasized to the parotid gland; this type of lesion is extremely rare and highly worthy of consideration because the authors misdiagnosed it.
ABSTRACT
Development of highly efficient, heavy-metal-free electrochemiluminescence (ECL) materials is attractive but still challenging. Herein, we report an aggregation-induced delayed ECL (AIDECL) active organic dot (OD) composed of a tert-butoxy-group-substituted benzophenone-dimethylacridine compound, which shows high ECL efficiency. The resultant ODs exhibit 2.1-fold higher ECL efficiency compared to control AIDECL-active ODs. Molecular stacking combined with theoretical calculations suggests that tert-butoxy groups effectively participate in the intermolecular interactions, further inhibiting the molecular motions in the aggregated states and thus accelerating radiative decay. On the basis of these ODs exhibiting excellent ECL performance, a proof-of-concept biosensor is constructed for the detection of miR-16 associated with Alzheimer's disease, which demonstrates excellent detection ability with the limit of detection of 1.7 fM. This work provides a new approach to improve the ECL efficiency and enriches the fundamental understanding of the structure-property relationship.
ABSTRACT
Intracellular cancer-related biomarker imaging strategy has been used for specific identification of cancer cells, which was of great importance to accurate cancer clinical diagnosis and prognosis studies. Localized DNA circuits with improved sensitivity showed great potential for intracellular biomarkers imaging. However, the ability of localized DNA circuits to specifically image cancer cells is limited by off-site signal leakage associated with a single-biomarker sensing strategy. Herein, we integrated the endogenous enzyme-powered strategy with logic-responsive and localized signal amplifying capability to construct a self-assembled endogenously AND logic DNA nanomachine (EDN) for highly specific cancer cell imaging. When the EDN encountered a cancer cell, the overexpressed DNA repairing enzyme apurinic/apyrimidinic endonuclease 1 (APE1) and miR-21 could synergistically activate a DNA circuit via cascaded localized toehold-mediated strand displacement (TMSD) reactions, resulting in amplified fluorescence resonance energy transfer (FRET) signal. In this strategy, both endogenous APE1 and miR-21, served as two "keys" to activate the AND logic operation in cancer cells to reduce off-tumor signal leakage. Such a multiplied molecular recognition/activation nanomachine as a powerful toolbox realized specific capture and reliable imaging of biomolecules in living cancer cells.
Subject(s)
DNA-(Apurinic or Apyrimidinic Site) Lyase , DNA , Fluorescence Resonance Energy Transfer , MicroRNAs , Humans , MicroRNAs/analysis , MicroRNAs/metabolism , DNA/chemistry , DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism , Neoplasms/diagnostic imaging , Optical ImagingABSTRACT
Achieving sensitive detection and accurate identification of cancer cells is vital for diagnosing and treating the disease. Here, we developed a logic signal amplification system using DNA tetrahedron-mediated three-dimensional (3D) DNA nanonetworks for sensitive electrochemiluminescence (ECL) detection and subtype identification of cancer cells. Specially designed hairpins were integrated into DNA tetrahedral nanostructures (DTNs) to perform a catalytic hairpin assembly (CHA) reaction in the presence of target microRNA, forming hyperbranched 3D nanonetworks. Benefiting from the "spatial confinement effect," the DNA tetrahedron-mediated catalytic hairpin assembly (DTCHA) reaction displayed significantly faster kinetics and greater cycle conversion efficiency than traditional CHA. The resulting 3D nanonetworks could load a large amount of Ru(phen)32+, significantly enhancing its ECL signal, and exhibit detection limits for both miR-21 and miR-141 at the femtomolar level. The biosensor based on modular logic gates facilitated the distinction and quantification of cancer cells and normal cells based on miR-21 levels, combined with miR-141 levels, to further identify different subtypes of breast cancer cells. Overall, this study provides potential applications in miRNA-related clinical diagnostics.
Subject(s)
Biosensing Techniques , Electrochemical Techniques , Luminescent Measurements , MicroRNAs , Humans , MicroRNAs/analysis , Electrochemical Techniques/methods , Biosensing Techniques/methods , DNA/chemistry , Nanostructures/chemistry , Limit of Detection , Cell Line, Tumor , Breast Neoplasms/diagnosis , MCF-7 CellsABSTRACT
Effective bimetallic nanoelectrocatalysis demands precise control of composition, structure, and understanding catalytic mechanisms. To address these challenges, we employ a two-in-one approach, integrating online synthesis with real-time imaging of bimetallic Au@Metal core-shell nanoparticles (Au@M NPs) via electrochemiluminescence microscopy (ECLM). Within 120 s, online electrodeposition and in situ catalytic activity screening alternate. ECLM captures transient faradaic processes during potential switches, visualizes electrochemical processes in real-time, and tracks catalytic activity dynamics at the single-particle level. Analysis using ECL photon flux density eliminates size effects and yields quantitative electrocatalytic activity results. Notably, a nonlinear activity trend corresponding to the shell metal to Au surface atomic ratio is discerned, quantifying the optimal surface component ratio of Au@M NPs. This approach offers a comprehensive understanding of catalytic behavior during the deposition process with high spatiotemporal resolution, which is crucial for tailoring efficient bimetallic nanocatalysts for diverse applications.
ABSTRACT
Electrochemistry that empowers innovative nanoscopic analysis has long been pursued. Here, the concept of aggregation-enabled electrochemistry (AEE) in a confined nanopore is proposed and devised by reactive oxygen species (ROS)-responsive aggregation of CdS quantum dots (QDs) within a functional nanopipette. Complementary Faradaic and non-Faradaic operations of the CdS QDs aggregate could be conducted to simultaneously induce the signal-on of the photocurrents and the signal-off of the ionic signals. Such a rationale permits the cross-checking of the mutually corroborated signals and thus delivers more reliable results for single-cell ROS analysis. Combined with the rich biomatter-light interplay, the concept of AEE can be extended to other stimuli-responsive aggregations for electrochemical innovations.
ABSTRACT
Subcellular metabolomics analysis is crucial for understanding intracellular heterogeneity and accurate drug-cell interactions. Unfortunately, the ultra-small size and complex microenvironment inside the cell pose a great challenge to achieving this goal. To address this challenge, we propose an artificial intelligence-assisted subcellular mass spectrometry imaging (AI-SMSI) strategy with in situ image segmentation. Based on the nanometer-resolution MSI technique, the protonated guanine and threonine ions were respectively employed as the nucleus and cytoplasmic markers to complete image segmentation at the subcellular level, avoiding mutual interference of signals from various compartments in the cell. With advanced AI models, the metabolites within the different regions could be further integrated and profiled. Through this method, we decrypted the distinct action mechanism of isomeric drugs, doxorubicin (DOX) and epirubicin (EPI), only with a stereochemical inversion at C-4'. Within the cytoplasmic region, fifteen specific metabolites were discovered as biomarkers for distinguishing the drug action difference between DOX and EPI. Moreover, we identified that the downregulations of glutamate and aspartate in the malate-aspartate shuttle pathway may contribute to the higher paratoxicity of DOX. Our current AI-SMSI approach has promising applications for subcellular metabolomics analysis and thus opens new opportunities to further explore drug-cell specific interactions for the long-term pursuit of precision medicine.
ABSTRACT
This work reports the construction of a miniaturized Ag/AgCl nanoelectrode on a nanopipette, which is capable of dual-functions of single-cell drug infusion and chloride detection and is envisioned to promote the study of chloride-correlated therapeutic effects.
Subject(s)
Chlorides , Silver Compounds , SilverABSTRACT
This study explores plasmon-induced electrochemical reactions on single nanoparticles using electrogenerated chemiluminescence microscopy (ECLM). Under laser irradiation, real-time screening showed lower plasmon-induced reaction efficiency for bimetallic Au@Pt nanoparticles compared to monometallic Au nanoparticles. ECLM offers a high-throughput imaging and precise quantitative approach for analyzing photo-electrochemical conversion at single nanoparticle level, valuable for both theoretical exploration and optimization of plasmonic nanocatalysts.
ABSTRACT
BACKGROUND: Triple-negative breast cancer (TNBC) is a malignant tumor without specific therapeutic targets and a poor prognosis. Chemotherapy is currently the first-line therapeutic option for TNBC. However, due to the heterogeneity of TNBC, not all of TNBC patients are responsive to chemotherapeutic agents. Therefore, the demand for new targeted agents is critical. ß-tubulin isotype III (Tubb3) is a prognostic factor associated with cancer progression, including breast cancer, and targeting Tubb3 may lead to improve TNBC disease control. Shikonin, the active compound in the roots of Lithospermun erythrorhizon suppresses the growth of various types of tumors, and its efficacy can be improved by altering its chemical structure. PURPOSE: In this work, the anti-TNBC effect of a shikonin derivative (PMMB276) was investigated, and its mechanism was also investigated. STUDY DESIGN/METHODS: This study combines flow cytometry, immunofluorescence staining, immunoblotting, immunoprecipitation, siRNA silencing, and the iTRAQ proteomics assay to analyze the inhibition potential of PMMB276 on TNBC. In vivo study was performed, Balb/c female murine models with or without the small molecule treatments. RESULTS: Herein, we screened 300 in-house synthesized analogs of shikonin against TNBC and identified a novel small molecule, PMMB276; it suppressed cell proliferation, induced apoptosis, and arrested the cell cycle at the G2/M phase, suggesting that it could have a tumor suppressive role in TNBC. Tubb3 was identified as the target of PMMB276 using proteomic and biological activity analyses. Meanwhile, PMMB276 regulated microtubule dynamics in vitro by inducing microtubule depolymerization and it could act as a tubulin stabilizer by a different process than that of paclitaxel. Moreover, suppressing or inhibiting Tubb3 with PMMB276 reduced the growth of breast cancer in an experimental mouse model, indicating that Tubb3 plays a significant role in TNBC progression. CONCLUSION: The findings support the therapeutic potential of PMMB276, a Tubb3 inhibitor, as a treatment for TNBC. Our findings might serve as a foundation for the utilization of shikonin and its derivatives in the development of anti-TNBC.
Subject(s)
Naphthoquinones , Triple Negative Breast Neoplasms , Humans , Female , Animals , Mice , Cell Line, Tumor , Triple Negative Breast Neoplasms/pathology , Tubulin , Proteomics , Cell ProliferationABSTRACT
Herein, the first iontronic photoelectrochemical (PEC) biorecognition probing is devised by rational engineering of a dual-functional bioconjugate, i.e., a light-sensitive intercalated structural DNA, as a smart gating module confined within a nanotip, which could respond to both the incident light and biotargets of interest. Light stimulation of the bioconjugate could intensify the negative charge at the nano-orifice to sustain enhanced ionic current. The presence of proteins (e.g., acetylcholinesterase, AChE) or nucleic acids (e.g., microRNA (miR)-10b) could lead to bioconjugate release with altered ionic signaling. The practical applicability of the methodology is confirmed by AChE detection in human serum and miR-10b detection in single cells.
Subject(s)
Biosensing Techniques , MicroRNAs , Humans , Acetylcholinesterase/chemistry , Biosensing Techniques/methods , Electrochemical Techniques/methods , DNAABSTRACT
Developing nanoscale ratiometric techniques capable of biochemical response should prove of significance for precise applications with stringent spatial and biological restrictions. Here we present and devise the concept of θ-nanopore ratiometry, which uses ratiometric signals that could well address the serious concerns about device deviation in fabrication and nonspecific adsorption in the detection. As exemplified by a 200 nm θ-nanopore toward miRNA detection, the ±20 nm aperture drift could be mitigated and the issue of nonspecific adsorption could be minimized in the complex cytosolic environment. Practical application of this θ-nanopore ratiometry realizes the measurements of cytosolic miRNA-10b. This work has not only established a nanoscopic ratiometric technique but also enriched the extant armory of nanotools for single-cell studies and beyond.
Subject(s)
Biosensing Techniques , MicroRNAs , NanoporesABSTRACT
Prokaryotic Argonautes (pAgos) have been recently used in many nucleic acid biosensing applications but have rarely been used for regulating the isothermal amplification system. Herein, we reported Thermus thermophilus Argonaute (TtAgo)-mediated background-suppressed exponential isothermal amplification (EXPAR) as the first example to explore the binding activity of pAgos toward regulation of the amplification template. It was demonstrated that thermophilic pAgos efficiently eliminated nonspecific hybridization between templates by their binding affinity with the template, resulting in greatly enhancing the specificity of EXPAR. TtAgo-mediated, background-suppressed EXPAR was employed to detect miRNA with a detection limit of 10-15 M, which was 1000 times and 100 times more sensitive than that of traditional RT-PCR and EXPAR, respectively. This method further showed good performance in discriminating cancer patients from healthy individuals, indicating its potential for practical clinical applications.
Subject(s)
MicroRNAs , Humans , MicroRNAs/analysis , Nucleic Acid Hybridization , Nucleic Acid Amplification Techniques/methodsABSTRACT
Small frame nucleic acids (FNAs) serve as excellent carrier materials for various functional nucleic acid molecules, showcasing extensive potential applications in biomedicine development. The carrier module and function module combination is crucial for probe design, where an improper combination can significantly impede the functionality of sensing platforms. This study explores the effect of various combinations on the sensing performance of nanodevices through simulations and experimental approaches. Variances in response velocities, sensitivities, and cell uptake efficiencies across different structures are observed. Factors such as the number of functional molecules loaded, loading positions, and intermodular distances affect the rigidity and stability of the nanostructure. The findings reveal that the structures with full loads and moderate distances between modules have the lowest potential energy. Based on these insights, a multisignal detection platform that offers optimal sensitivity and response speed is developed. This research offers valuable insights for designing FNAs-based probes and presents a streamlined method for the conceptualization and optimization of DNA nanodevices.
Subject(s)
MicroRNAs , Nanostructures , Nucleic Acids , MicroRNAs/genetics , DNA/chemistry , Nanostructures/chemistry , Computer Simulation , Nanotechnology/methodsABSTRACT
INTRODUCTION: The increasing number of studies have shown that Lycium barbarum polysaccharides possess anti-tumor effects. However, the determination of the active ingredients and their mechanism against melanoma inhibition are still unknown. METHODS: In this study, we aimed to investigate the mechanisms of action of Lycium barbarum active glycopeptide (LBAG) on melanoma. LBAG was extracted and isolated from the fruit of Lycium barbarum using aqueous alcoholic precipitation and identified using ultra-performance liquid chromatography-quadrupole-time of flightmass spectrometry. Various assays including cell apoptosis, cell cycle analysis, colony formation assay, cell scratch test, flow cytometry, and Western blot were performed to evaluate the effects of LBAG on melanoma. RESULTS: The results showed that LBAG has a molecular weight of 10-15 kDa and contains Man, Rha, GlcA, Glc, Gal, and Ara18 amino acids. Treatment with LBAG significantly decreased B16 cell proliferation and induced cell cycle arrest at the G0/G phase, accompanied by the accumulation of reactive oxygen species. Western blot analysis revealed that the phosphorylation of P38-MAPK and AKT, as well as the expression of N-acetyl-Lcysteine, were related to cell apoptosis and cell cycle regulation. In mouse xenografts, LBAG inhibited tumor growth through the P38-MAPK and AKT signaling pathways. CONCLUSION: In conclusion, the anti-melanoma activity of LBAG may induce apoptosis in cancer cells through ROSmediated activation of the P38-MAPK and AKT signaling pathways. These findings provide a foundation for further research on the anti-melanoma potential of LBAG.