High Dynamic Range Probing of Single-Molecule Mechanical Force Transitions at Cell-Matrix Adhesion Bonds by a Plasmonic Tension Nanosensor.

Mechanical signals in animal tissues are complex and rapidly changed, and how the force transduction emerges from the single-cell adhesion bonds remains unclear. DNA-based molecular tension sensors (MTS), albeit successful in cellular force probing, were restricted by their detection range and temporal resolution. Here, we introduced a plasmonic tension nanosensor (PTNS) to make straight progress toward these shortcomings. Contrary to the fluorescence-based MTS that only has specific force response thresholds, PTNS enabled the continuous and reversible force measurement from 1.1 to 48 pN with millisecond temporal resolution. We used the PTNS to visualize the high dynamic range single-molecule force transitions at cell-matrix adhesions during adhesion formation and migration. Time-resolved force traces revealed that the lifetime and duration of stepwise force transitions of molecular clutches are strongly modulated by the traction force through filamentous actin. The force probing technique is sensitive, fast, and robust and constitutes a potential tool for single-molecule and single-cell biophysics.

Autocrine phosphatase PDP2 inhibits ferroptosis by dephosphorylating ACSL4 in the Luminal A Breast Cancer.

Phosphatases can dephosphorylate phosphorylated kinases, leading to their inactivation, and ferroptosis is a type of cell death. Therefore, our aim is to identify phosphatases associated with ferroptosis by analyzing the differentially expressed genes (DEGs) of the Luminal A Breast Cancer (LumABC) cohort from the Cancer Genome Atlas (TCGA). An analysis of 260 phosphatase genes from the GeneCard database revealed that out of the 28 DEGs with high expression, only the expression of pyruvate dehydrogenase phosphatase 2 (PDP2) had a significant correlation with patient survival. In addition, an analysis of DEGs using gene ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis revealed a significant variation in the expression of ferroptosis-related genes. To further investigate this, we analyzed 34 ferroptosis-related genes from the TCGA-LumABC cohort. The expression of long-chain acyl-CoA synthetase 4 (ACSL4) was found to have the highest correlation with the expression of PDP2, and its expression was also inversely proportional to the survival rate of patients. Western blot experiments using the MCF-7 cell line showed that the phosphorylation level of ACSL4 was significantly lower in cells transfected with the HA-PDP2 plasmid, and ferroptosis was correspondingly reduced (p < 0.001), as indicated by data from flow cytometry detection of membrane-permeability cell death stained with 7-aminoactinomycin, lipid peroxidation, and Fe2+. Immunoprecipitation experiments further revealed that the phosphorylation level of ACSL4 was only significantly reduced in cells where PDP2 and ACSL4 co-precipitated. These findings suggest that PDP2 may act as a phosphatase to dephosphorylate and inhibit the activity of ACSL4, which had been phosphorylated and activated in LumABC cells. Further experiments are needed to confirm the molecular mechanism of PDP2 inhibiting ferroptosis.

Quantifying source contributions to ambient NH3 using Geo-AI with time lag and parcel tracking functions.

Ambient ammonia (NH3) plays an important compound in forming particulate matters (PMs), and therefore, it is crucial to comprehend NH3's properties in order to better reduce PMs. However, it is not easy to achieve this goal due to the limited range/real-time NH3 data monitored by the air quality stations. While there were other studies to predict NH3 and its source apportionment, this manuscript provides a novel method (i.e., GEO-AI)) to look into NH3 predictions and their contribution sources. This study represents a pioneering effort in the application of a novel geospatial-artificial intelligence (Geo-AI) base model with parcel tracking functions. This innovative approach seamlessly integrates various machine learning algorithms and geographic predictor variables to estimate NH3 concentrations, marking the first instance of such a comprehensive methodology. The Shapley additive explanation (SHAP) was used to further analyze source contribution of NH3 with domain knowledge. From 2016 to 2018, Taichung's hourly average NH3 values were predicted with total variance up to 96%. SHAP values revealed that waterbody, traffic and agriculture emissions were the most significant factors to affect NH3 concentrations in Taichung among all the characteristics. Our methodology is a vital first step for shaping future policies and regulations and is adaptable to regions with limited monitoring sites.

Lipid concentration and composition in xylem sap of woody angiosperms from a tropical savanna and a seasonal rainforest.

Lipids may play an important role in preventing gas embolisms by coating nanobubbles in xylem sap. Few studies on xylem sap lipids have been reported for temperate plants, and it remain unclear whether sap lipids have adaptational significance in tropical plants. In this study, we quantify the lipid composition of xylem sap for angiosperm species from a tropical savanna (seven species) and a seasonal rainforest (five species) using mass spectrometry. We found that all twelve species studied contained lipids in their xylem sap, including galactolipids, phospholipids and triacylglycerol, with a total lipid concentration ranging from 0.09 to 0.26 nmol/L. There was no difference in lipid concentration or composition between plants from the two sites, and the lipid concentration was negatively related to species' open vessel volume. Furthermore, savanna species showed little variation in lipid composition between the dry and the rainy season. These results support the hypothesis that xylem sap lipids are derived from the cytoplasm of individual conduit cells, remain trapped inside individual conduits, and undergo few changes in composition over consecutive seasons. A xylem sap lipidomic data set, which includes 12 tropical tree species from this study and 11 temperate tree species from literature, revealed no phylogenetic signals in lipid composition for these species. This study fills a knowledge gap in the lipid content of xylem sap in tropical trees and provides additional support for their common distribution in xylem sap of woody angiosperms. It appears that xylem sap lipids have no adaptive significance.

Prolonged near-infrared fluorescence imaging of microRNAs and proteases in vivo by aggregation-enhanced emission from DNA-AuNC nanomachines.

Developing a comprehensive strategy for imaging various biomarkers (i.e., microRNAs and proteases) in vivo is an exceptionally formidable task. Herein, we have designed a deoxyribonucleic acid-gold nanocluster (DNA-AuNC) nanomachine for detecting tumor-related TK1 mRNA and cathepsin B in living cells and in vivo. The DNA-AuNC nanomachine is constructed using AuNCs and DNA modules that incorporate a three component DNA hybrid (TD) and a single-stranded fuel DNA (FD). Upon being internalized into tumor cells, the TK1 mRNA initiates the DNA-AuNC nanomachine through DNA strand displacement cascades, leading to the amplified self-assembly and the aggregation-enhanced emission of AuNCs for in situ imaging. Furthermore, with the aid of a protease nanomediator consisting of a mediator DNA/peptide complex and AuNCs (DpAuNCs), the DNA-AuNC nanomachine can be triggered by the protease-activated disassembly of the DNA/peptide complex on the nanomediator, resulting in the aggregation of AuNCs for in vivo protease amplified detection. It is worth noting that our study demonstrates the impressive tumor permeability and accumulation capabilities of the DNA-AuNC nanomachines via in situ amplified self-assembly, thereby facilitating prolonged imaging of TK1 mRNA and cathepsin B both in vitro and in vivo. This strategy presents a versatile and biomarker-specific paradigm for disease diagnosis.

Unraveling assemblage of microbial community dwelling in Dabaoshan As/Pb/Zn mine-impacted area: A typical mountain mining area of South China.

Microbial community assemblage includes microorganisms from the three domains including Bacteria, Archaea, and Eukarya (Fungi), which play a crucial role in geochemical cycles of metal(loid)s in mine tailings. Mine tailings harbor vast proportions of metal(loid)s, representing a unique source of co-contamination of metal(loid)s that threaten the environment. The elucidation of the assembly patterns of microbial communities in mining-impacted ecospheres has received little attention. To decipher the microbial community assembly processes, the microbial communities from the five sites of the Dabaoshan mine-impacted area were profiled by the MiSeq sequencing of 16S rRNA (Bacteria and Archaea) genes and internal transcribed spacers (Fungi). Results indicated that the coexistence of 31 bacterial, 10 fungal, and 3 archaeal phyla, were mainly dominated by Mucilaginibacter, Cladophialophora, and Candidatus Nitrosotalea, respectively. The distribution of microorganisms was controlled by deterministic processes. The combination of Cu, Pb, and Sb was the main factor explaining the structure of microbial communities. Functional predicting analysis of bacteria and archaea based on the phylogenetic investigation of communities by reconstruction of unobserved states analyses revealed that the metabolic pathways related to arsenite transporter, arsenate reductase, and FeS cluster were important for metal detoxification. Furthermore, the ecological guilds (pathogens, symbiotrophs, and saprotrophs) of fungal communities explained 44.5 % of functional prediction. In addition, metal-induced oxidative stress may be alleviated by antioxidant enzymes of fungi communities, such as catalase. Such information provides new insights into the microbial assembly rules in co-contaminated sites.

Quality Control of Mass-Encoded Nanodevices by Compartmented DNA Origami Frames for Precision Information Coding and Logic Mapping.

Encoded nanostructures afford an ideal platform carrying multi-channel signal components for multiplexed assay and information security. However, with the demand on exclusivity and reproducibility of coding signals, precise control on the structure and composition of nanomaterials featuring fully distinguishable signals remains challenging. By using the multiplexing capability of mass spectrometry (MS) and spatial addressability of DNA origami nanostructures, we herein propose a quality control methodology for constructing mass-encoded nanodevices (namely MNTs-TDOFs) in the scaffold of compartmented tetrahedral DNA origami frames (TDOFs), in which the arrangement and stoichiometry of four types of mass nanotags (MNTs) can be finely regulated and customized to generate characteristic MS patterns. The programmability of combinatorial MNTs and orthogonality of individual compartments allows further evolution of MNTs-TDOFs to static tagging agents and dynamic nanoprobes for labeling and sensing of multiple targets. More importantly, structure control at single TDOF level ensures the constancy of prescribed MS outputs, by which a high-capacity coding system was established for secure information encryption and decryption. In addition to the multiplexed outputs in parallel, the nanodevices could also map logic circuits with interconnected complexity and logic events of c-Met recognition and dimerization on cell surface for signaling regulation by MS interrogation.

Aggregation-Induced Enhanced Electrochemiluminescence from Tris(bipyridine)ruthenium(II) Derivative Nanosheets for the Ultrasensitive Detection of Human Telomerase RNA.

The traditional tris(bipyridine)ruthenium(II) complex suffers from the notorious aggregation-caused quenching effect, which greatly compromises its electrochemiluminescence (ECL) efficiency, thus hindering further applications in biosensing and clinical diagnosis. Here, the ultrathin tetraphenylethylene-active tris(bipyridine)ruthenium(II) derivative nanosheets (abbreviated as Ru-TPE NSs) are synthesized through a protein-assisted self-assembly strategy for ultrasensitive ECL detection of human telomerase RNA (hTR) for the first time. The synthesized Ru-TPE NSs exhibit the aggregation-induced enhanced ECL behavior and excellent water-dispersion. Surprisingly, up to a 106.5-fold increase in the ECL efficiency of Ru-TPE NSs is demonstrated compared with the dispersed molecules in an organic solution. The restriction of intramolecular motions is confirmed to be responsible for the significant ECL enhancement. Therefore, this proposed ECL biosensor shows high sensitivity and excellent selectivity for hTR based on Ru-TPE NSs as efficient ECL beacons and the catalytic hairpin assembly as signal amplification, whose detection limit is as low as 8.0 fm, which is far superior to the previously reported works. Here, a promising analytical method is provided for early clinical diagnosis and a new type of efficient ECL emitters with great application prospects is represented.

Confinement in Dual-Chain-Locked DNA Origami Nanocages Programs Marker-Responsive Delivery of CRISPR/Cas9 Ribonucleoproteins.

Delivery of CRISPR/Cas9 ribonucleoproteins (RNPs) offers a powerful tool for therapeutic genome editing. However, precise manipulation of CRISPR/Cas9 RNPs to switch the machinery on and off according to diverse disease microenvironments remains challenging. Here, we present dual-chain-locked DNA origami nanocages (DL-DONCs) that can confine Cas9 RNPs in the inner cavity for efficient cargo delivery and dual-marker-responsive genome editing in the specified pathological states. By engineering of ATP or miRNA-21-responsive dsDNAs as chain locks on the DONCs, the permeability of nanocages and accessibility of encapsulated Cas9 RNPs can be finely regulated. The resulting DL-DONCs enabled steric protection of bioactive Cas9 RNPs from premature release and deactivation during transportation while dismounting the dual chain locks in response to molecular triggers after internalization into tumor cells, facilitating the escape of Cas9 RNPs from the confinement for gene editing. Due to the dual-marker-dominated uncaging mechanism, the gene editing efficiency could be exclusively determined by the combined level of ATP and miRNA-21 in the target cellular environment. By targeting the tumor-associated PLK-1 gene, the DL-DONCs-enveloped Cas9 RNPs have demonstrated superior inhibitory effects on the proliferation of tumor cells in vitro and in vivo. The developed DL-DONCs provide a custom-made platform for the precise manipulation of Cas9 RNPs, which can be potentially applied to on-demand gene editing for classified therapy in response to arbitrary disease-associated biomolecules.

Cu-based catalyst designs in CO2 electroreduction: precise modulation of reaction intermediates for high-value chemical generation.

The massive emission of excess greenhouse gases (mainly CO2) have an irreversible impact on the Earth's ecology. Electrocatalytic CO2 reduction (ECR), a technique that utilizes renewable energy sources to create highly reduced chemicals (e.g. C2H4, C2H5OH), has attracted significant attention in the science community. Cu-based catalysts have emerged as promising candidates for ECR, particularly in producing multi-carbon products that hold substantial value in modern industries. The formation of multi-carbon products involves a range of transient intermediates, the behaviour of which critically influences the reaction pathway and product distribution. Consequently, achieving desirable products necessitates precise regulation of these intermediates. This review explores state-of-the-art designs of Cu-based catalysts, classified into three categories based on the different prospects of the intermediates' modulation: heteroatom doping, morphological structure engineering, and local catalytic environment engineering. These catalyst designs enable efficient multi-carbon generation in ECR by effectively modulating reaction intermediates.

Molecular detection of Bartonella species in wild small mammals in western Yunnan Province, China.

Background: Small mammals serve as the main reservoir for Bartonella and as a proxy indicator of the potential risk of Bartonella transmission from nature to humans. They offer a valuable early warning for human infection. Nevertheless, geographical variations in the impact of the host on the occurrence of Bartonella infection are underestimated. This study was designed to investigate the infection characteristics of Bartonella and explore its species diversity in wild small mammals in western Yunnan Province, China. Methods: Wild small mammals were captured from Yulong, Jianchuan, and Lianghe counties in western Yunnan Province between 2015 and 2016. Real-time quantitative PCR (qPCR) was used to detect Bartonella infection, and the Bartonella species were identified by phylogenetic analysis. The factors associated with Bartonella infection in small mammals were analyzed by the Chi-square Test. Results: The prevalence of Bartonella in small mammals was 47.85% (768/1605). Lianghe County had the highest Bartonella infection rate, with 56.27% of the samples tested positive, followed by a rate of 50.91% was tested in Yulong County, and 39.97% in Jianchuan County (p < 0.001). Bartonella was detected positive in a total 25 small mammal species, with infection rates ranging from 2.17% to 100%. Niviventer fulvescens had the highest Bartonella infection rate. In comparison with the dominant small mammal species, Eothenomys mileyus had the lowest Bartonella infection rate than that in Apodemus chevrieri, Rattus tanezumi, and Apodemus draco (p < 0.001). Male small mammals had a higher infection rate than females (p < 0.05). The prevalence of Bartonella in small mammals during the summer season was higher compared to the other three seasons (p < 0.001). Woodland landscape had the highest Bartonella infection rate (p < 0.001). Bartonella rochalimae, B. japonica, B. tribocorum, B. washoensis, B. sylvatica, and B. rattimassiliensis were obtained from infected small mammals. Conclusion: This study showed a high prevalence of Bartonella was detected with various Bartonella species in small mammals in Yulong, Jianchuan, and Lianghe counties of western Yunnan Province. These findings hold significant scientific clues, providing valuable reference points for further research of Bartonella natural foci in Yunnan or other analogues environments.

High-performance SERS chips for sensitive identification and detection of antibiotic residues with self-assembled hollow Ag octahedra.

High-performance SERS chips via self-assembled hollow Ag octahedra on PDMS were employed to achieve the sensitive identification and detection of antibiotic residues. The developed SERS chips were successfully applied in the detection of ciprofloxacin (CIP), amoxicillin (AMX) and cefazolin (CZL) in wastewater and tap water samples, as well as enrofloxacin (ENR) in milk, demonstrating the sensitive determination of antibiotics in the real environment. From this perspective, these SERS chips are expected to expand the on spot sensitive detection and identification field of antibiotic residues.

Cell-Derived N/P/S-Codoped Fluorescent Carbon Nanodots with Intrinsic Targeting Ability for Tumor-Specific Phototheranostics.

Combining targeting ability, imaging function, and photothermal/photodynamic therapy into a single agent is highly desired for cancer theranostics. Herein, we developed a one-for-all nanoplatform with N/P/S-codoped fluorescent carbon nanodots (CNDs) for tumor-specific phototheranostics. The CNDs were prepared via a one-pot hydrothermal process using cancer cells as sources of carbon, nitrogen, phosphorus, and sulfur. The obtained N/P/S-codoped CNDs exhibit wide light absorption in the range of 200-900 nm and excitation-dependent emission with high photostability. Importantly, the cancer cell-derived N/P/S-codoped CNDs have outstanding biocompatibility and naturally intrinsic targeted ability for cancer cells as well as dual photothermal/photodynamic effects under 795 nm laser irradiation. Moreover, the photothermal conversion efficiency and singlet oxygen (1O2) generation efficiency were calculated to be 52 and 34%, respectively. These exceptional properties enable CNDs to act as fine theranostic agents for targeted imaging and photothermal-photodynamic synergistic therapy within the NIR therapeutic window. The CNDs prepared in this work are promising for construction as a universal tumor phototheranostic platform.

Advances of Electrochemical and Electrochemiluminescent Sensors Based on Covalent Organic Frameworks.

Covalent organic frameworks (COFs), a rapidly developing category of crystalline conjugated organic polymers, possess highly ordered structures, large specific surface areas, stable chemical properties, and tunable pore microenvironments. Since the first report of boroxine/boronate ester-linked COFs in 2005, COFs have rapidly gained popularity, showing important application prospects in various fields, such as sensing, catalysis, separation, and energy storage. Among them, COFs-based electrochemical (EC) sensors with upgraded analytical performance are arousing extensive interest. In this review, therefore, we summarize the basic properties and the general synthesis methods of COFs used in the field of electroanalytical chemistry, with special emphasis on their usages in the fabrication of chemical sensors, ions sensors, immunosensors, and aptasensors. Notably, the emerged COFs in the electrochemiluminescence (ECL) realm are thoroughly covered along with their preliminary applications. Additionally, final conclusions on state-of-the-art COFs are provided in terms of EC and ECL sensors, as well as challenges and prospects for extending and improving the research and applications of COFs in electroanalytical chemistry.

Enhancing charge transfer in a W18O49/g-C3N4 heterostructure via band structure engineering for effective SERS detection and flexible substrate applications.

Chemical mechanism (CM)-related surface-enhanced Raman spectroscopy (SERS) has received tremendous interest due to its exceptional stability and excellent uniformity. Nevertheless, there remains a demand for ingenious methodologies for promoting effective charge transfer (CT) to improve SERS sensitivity further. Herein, a band structure engineered W18O49/g-C3N4 heterostructure (WCN) was first employed as a CM-based SERS substrate with remarkable enhancement and sensitivity. To investigate the Raman enhancement properties of the substrate, malachite green (MG) was employed as the Raman probe with the excitation of a 633 nm laser. The WCN substrate exhibits a Raman enhancement factor (EF) of 2.6 × 107, achieving a limit of detection (LOD) of 1.9 × 10-10 M for MG. The outstanding Raman amplification behavior can be attributed to the heterojunction-induced efficient CT process, energy band matching resonance due to minor doping with g-C3N4 serving as a band gap modifier, and improved photo-induced charge transfer (PICT) efficiency via the oxygen vacancies in the W18O49 units. Additionally, a flexible SERS substrate based on WCN was constructed using a vacuum filtration method and utilized to detect prohibited pharmaceutical residues on fish skin. The integration of this WCN and a nylon membrane not only preserves the Raman activity of the WCN for sensitive detection but also endows the Raman substrate with high flexibility and good mechanical durability, making it a potential candidate for in situ detection in particular environments.

Complementary Homogeneous Electrochemical and Photothermal Dual-Modal Sensor for Highly Sensitive Detection of Organophosphorus Pesticides via Stimuli-Responsive COF/Methylene Blue@MnO2 Composite.

Credible and on-site detection of organophosphorus pesticides (OPs) in complex matrixes is significant for food security and environmental monitoring. Herein, a novel COF/methylene blue@MnO2 (COF/MB@MnO2) composite featured abundant signal loading, a specific recognition unit, and robust oxidase-like activity was successfully prepared through facile assembly processes. The multifunctional composite acted as a homogeneous electrochemical and photothermal dual-mode sensing platform for OPs detection through stimuli-responsive regulation. Without the presence of OPs, the surface MnO2 coating could recognize thiocholine (TCh), originating from acetylcholinesterase (AChE)-catalyzed hydrolysis of acetylthiocholine (ATCh), and exhibited a distinctly amplified diffusion current due to the release of plentiful MB; while the residual MnO2 nanosheets could only catalyze less TMB into oxidized TMB (oxTMB) with a typical near-infrared (NIR) absorption, enabling NIR-driven photothermal assay with a low temperature using a portable thermometer. Based on the inhibitory effect of OPs on AChE activity and OP-regulated generation of TCh, chlorpyrifos as a model target can be accurately detected with a low limit of detection of 0.0632 and 0.108 ng/mL by complementary electrochemical and photothermal measurements, respectively. The present dual-mode sensor was demonstrated to be excellent for application to the reliable detection of OPs in complex environmental and food samples. This work can not only provide a complementary dual-mode method for convenient and on-site detection of OPs in different scenarios but also expand the application scope of the COF-based multifunctional composite in multimodal sensors.

Site-selective heat boosting electrochemiluminescence for single cell imaging.

In operando visualization of local electrochemical reactions provides mechanical insights into the dynamic transport of interfacial charge and reactant/product. Electrochemiluminescence is a crossover technique that quantitatively determines Faraday current and mass transport in a straightforward manner. However, the sensitivity is hindered by the low collision efficiency of radicals and side reactions at high voltage. Here, we report a site-selective heat boosting electrochemiluminescence microscopy. By generating a micron-scale heat point in situ at the electrode-solution interface, we achieved an enhancement of luminescence intensity up to 63 times, along with an advance of 0.2 V in applied voltage. Experimental results and finite element simulation demonstrate that the fundamental reasons are accelerated reaction rate and thermal convection via a photothermal effect. The concentrated electrochemiluminescence not only boosts the contrast of single cells by 20.54 times but also enables the site-selective cell-by-cell analysis of the heterogeneous membrane protein abundance. This electrochemical visualization method has great potential in the highly sensitive and selective analysis of local electron transfer events.

PEC-SERS Dual-Mode Detection of Foodborne Pathogens Based on Binding-Induced DNA Walker and C3N4/MXene-Au NPs Accelerator.

In this paper, a photoelectrochemical (PEC)-surface-enhanced Raman scattering (SERS) dual-mode biosensor is constructed coupled with a dual-recognition binding-induced DNA walker with a carbon nitride nanosheet (C3N4)/MXene-gold nanoparticles (C/M-Au NPs) accelerator, which is reliable and capable for sensitive and accurate detection of Staphylococcus aureus (S. aureus). Initially, a photoactive heterostructure is formed by combining C3N4 and MXene via a simple electrostatic self-assembly as they possess well-matched band-edge energy levels. Subsequently, in situ growth of gold nanoparticles on the formed surface results in better PEC performance and SERS activity, because of the synergistic effects of surface plasmon resonance and Schottky barrier. Furthermore, a three-dimensional, bipedal, and dual-recognition binding-induced DNA walker is introduced with the formation of Pb2+-dependent DNAzyme. In the presence of S. aureus, a significant quantity of intermediate DNA (I-DNA) is generated, which can open the hairpin structure of Methylene Blue-tagged hairpin DNA (H-MB) on the electrode surface, thereby enabling the switch of signals for the quantitative determination of S. aureus. The constructed PEC-SERS dual-mode biosensor that can be mutually verified under one reaction effectively addresses the problem of the low detection accuracy of traditional sensors. Experimental results revealed that the effective combination of PEC and SERS is achieved for amplification detection of S. aureus with a detection range of 5-108 CFU/mL (PEC) and 10-108 CFU/mL (SERS), and a detection of limit of 0.70 CFU/mL (PEC) and 1.35 CFU/mL (SERS), respectively. Therefore, this study offers a novel and effective dual-mode sensing strategy, which has important implications for bioanalysis and health monitoring.

One-Pot Synthesis of Tumor-Microenvironment Responsive Degradable Nanoflower-Medicine for Multimodal Cancer Therapy with Reinvigorating Antitumor Immunity.

Multimodal cancer therapies show great promise in synergistically enhancing anticancer efficacy through different mechanisms. However, most current multimodal therapies either rely on complex assemblies of multiple functional nanomaterials and drug molecules or involve the use of nanomedicines with poor in vivo degradability/metabolizability, thus restricting their clinical translatability. Herein, a nanoflower-medicine using iron ions, thioguanine (TG), and tetracarboxylic porphyrin (TCPP) are synthesized as building blocks through a one-step hydrothermal method for combined chemo/chemodynamic/photodynamic cancer therapy. The resulting nanoflowers, consisting of low-density Fe2 O3 core and iron complex (Fe-TG and Fe-TCPP compounds) shell, exhibit high accumulation at the tumor site, desirable degradability in the tumor microenvironment (TME), robust suppression of tumor growth and metastasis, as well as effective reinvigoration of host antitumor immunity. Triggered by the low pH in tumor microenvironment, the nanoflowers gradually degrade after internalization, contributing to the effective drug release and initiation of high-efficiency catalytic reactions precisely in tumor sites. Moreover, iron ions can be eliminated from the body through renal clearance after fulfilling their mission. Strikingly, it is also found that the multimodal synergistic therapy effectively elicits the host antitumor immunity without inducing additional toxicity. This easy-manufactured and degradable multimodal therapeutic nanomedicine is promising for clinical precision oncology.

Intellectualized Visualization of Single-Particle Raman Spectra for Sensitive Detection and Simultaneous Multianalysis of Heavy Metal Ions.

Easy-to-use, reliable, and real-time methods for detecting heavy metal ion contamination are urgently required, which is a primary concern for water pollution control and human health. However, present methods for this aim are still unable to achieve simultaneous multianalysis for complex real sample detection. Herein, an intellectualized vision-based single-nanoparticle Raman imaging strategy combined with ion-responsive functional nucleic acids (FNAs) was proposed to address these issues. We reported a correspondence between the concentration of the analytes and the density of particles (DOP) of specifically captured nanoparticles to achieve sensitive detection and simultaneous multianalysis of heavy metal ions. The specific detection of Pb2+ (Hg2+) was obtained with a detection linear range from 100 pM to 100 nM (from 500 fM to 100 nM) and limit of detections low to 1 pM (100 fM), with the advantages of good specificity, excellent homogeneity, and reproducibility. Furthermore, the differentiation of different heavy metal ions (Pb2+/Hg2+) was achieved, i.e., the simultaneous multianalysis, based on Raman imaging of the single particle and intelligent machine vision method. Finally, the Raman imaging assay was utilized for real sample analysis, and it provided a powerful and reliable tool for detecting trace Pb2+/Hg2+ in real water samples and facilitated the portable on-site monitoring of heavy metal ions.