Multidimensional four-wave mixing signals detected by quantum squeezed light.

Four-wave mixing (FWM) of optical fields has been extensively used in quantum information processing, sensing, and memories. It also forms a basis for nonlinear spectroscopies such as transient grating, stimulated Raman, and photon echo where phase matching is used to select desired components of the third-order response of matter. Here we report an experimental study of the two-dimensional quantum noise intensity difference spectra of a pair of squeezed beams generated by FWM in hot Rb vapor. The measurement reveals details of the [Formula: see text] susceptibility dressed by the strong pump field which induces an AC Stark shift, with higher spectral resolution compared to classical measurements of probe and conjugate beam intensities. We demonstrate how quantum correlations of squeezed light can be utilized as a spectroscopic tool which unlike their classical counterparts are robust to external noise.

Homotypic Membrane-Enhanced Blood-Brain Barrier Crossing and Glioblastoma Targeting for Precise Surgical Resection and Photothermal Therapy.

The crossing of blood-brain barrier (BBB) is essential for glioblastoma (GBM) therapy, and homotypic targeting is an effective strategy to achieve BBB crossing. In this work, GBM patient-derived tumor cell membrane (GBM-PDTCM) is prepared to cloak gold nanorods (AuNRs). Relying on the high homology of the GBM-PDTCM to the brain cell membrane, GBM-PDTCM@AuNRs realize efficient BBB crossing and selective GBM targeting. Meanwhile, owing to the functionalization of Raman reporter and lipophilic fluorophore, GBM-PDTCM@AuNRs are able to generate fluorescence and Raman signals at GBM lesion, and almost all tumor can be precisely resected in 15 min by the guidance of dual signals, ameliorating the surgical treatment for advanced GBM. In addition, photothermal therapy for orthotopic xenograft mice is accomplished by intravenous injection of GBM-PDTCM@AuNRs, doubling the median survival time of the mice, which improves the nonsurgical treatment for early GBM. Therefore, benefiting from homotypic membrane-enhanced BBB crossing and GBM targeting, all-stage GBM can be treated with GBM-PDTCM@AuNRs in distinct ways, providing an alternative idea for the therapy of tumor in the brain.

Bio-Inspired Electrochemical Detection of Nitric Oxide Promoted by Coordinating the Histamine-Iron Phthalocyanine Catalytic Center on Microelectrode.

Biomimetic structures to fabricate bioelectronic interfaces that allow sensors to electrically communicate with electrodes have potential applications in the development of biosensors. Herein, inspired by the structure feature of nitric oxide (NO) sensory protein, we constructed a biomimetically catalytic center, the histamine coordinated iron phthalocyanine (FePc), for efficient and sensitive detection of NO. In specific, NO is recognized by axial tethered FePc, and the oxidative signal of NO on FePc is converted into output signal through electrocatalytic oxidation. Based on the fabricated catalytic structure on the carbon fiber electrode, on one hand, the macrocyclic π system of FePc enabled a rapid redox process, which facilitates electron transfer, thereby greatly improving sensitivity. On the other hand, by coordination with histamine on the electrode surface, FePc can enhance the electrochemical oxidation activity toward NO and promote catalytic detection, which have been revealed by electrochemical characterizations and density functional theory theoretical calculations. The designed electrochemical microsensor exhibits a low limit of detection (0.03 nM) and shows a wide detection range (0.1 nM-2 µM). In addition, the electrochemical microsensor has been successfully used for real-time monitoring of NO release by live cells. So, this work shows a new strategy for the design of bio-inspired electrochemical microsensors that may provide a potential analytical tool for tracing biological signal molecules with enzyme-free biomimetically catalytic centers.

Functionalized biological metal-organic framework with nanosized coronal structure and hierarchical wrapping pattern for enhanced targeting therapy.

Inefficient tumor-targeted delivery and uncontrolled drug release are the major obstacles in cancer chemotherapy. Herein, inspired by the targeting advantage of coronavirus from its size and coronal structure, a coronal biological metal-organic framework nanovehicle (named as corona-BioMOF) is constructed for improving its precise cancer targeting ability. The designed corona-BioMOF is constructed as the carriers-encapsulated carrier model by inner coated with abundant protein-nanocaged doxorubicin particles and external decorated with high-affinity apoferritin proteins to form the spiky surface for constructing the specific coronal structure. The corona-BioMOF shows a higher affinity and an enhanced targeting ability towards receptor-positive cancer cells compared to that of MOF-drug composites without spiky surface. It also exhibits the hierarchical wrapping pattern-endowed controlled lysosome-specific drug release and remarkable tumor lethality in vivo. Moreover, water-induced surface defect-based protein handle mechanism is first proposed to shape the coronal-BioMOF. This work will provide a better inspiration for nanovehicle construction and be broadly useful for clinical precision nanomedicine.

Characterization of four spliced isoforms of a transmembrane C-type lectin from Procambarus clarkii and their function in facilitating WSSV infection.

C-type lectin (CTL) is an important pattern recognition receptor that play vital functions in the innate immunity. Many soluble CTLs in crustacean participate in the inhibition or promotion of white spot syndrome virus (WSSV) infection. However, whether transmembrane CTLs participate in WSSV infection in crustacean remains unknown. In the present study, four spliced isoforms of a transmembrane CTL (designated as PcTlec) from Procambarus clarkii were identified for the first time. The genome structure of PcTlec contains eight exons, six known introns, and one unknown intron. PcTlec-isoform1 is produced by intron retention, whereas PcTlec-isoform3 and PcTlec-isoform4 are produced by exon skipping. All of them contain the transmembrane domain and characteristic carbohydrate recognition domain (CRD). Four PcTlec isoforms were mainly expressed in the hepatopancreas, stomach, and intestine. After WSSV challenge, the expression levels of PcTlec-isoform1-4 in the intestine were upregulated. The knockdown of the region shared by four PcTlec isoforms evidently decreased the expression of WSSV envelope protein VP28 and the copies of viral particles. A recombinant protein (rPcTlec-CRD) containing the CRD that was shared by four PcTlec isoforms was acquired by procaryotic expression system. The injection of purified rPcTlec-CRD protein evidently increased the VP28 expression and WSSV copies during viral infection. Moreover, rPcTlec-CRD could directly bind to WSSV and interact with VP28 protein. These findings indicate that new-found transmembrane CTL isoforms in P. clarkii may act as viral receptors that facilitate WSSV infection. This study contributes to the recognition and understanding of the functions of transmembrane CTLs in crustacean in the infection of host by WSSV.

Co-Quenching Effect between Lanthanum Metal-Organic Frameworks Luminophore and Crystal Violet for Enhanced Electrochemiluminescence Gene Detection.

Exploring new electrochemiluminescence (ECL) luminophores to construct high-efficiency sensing systems is always a hot direction for developing ECL sensors. Compared with other luminophores, metal-organic frameworks (MOFs) exhibit high mass transfer ability for accelerating the reactivity in its pore channels, which is conducive to improving the performance of ECL sensors. In this work, La3+ -BTC MOFs (LaMOFs) are prepared as the highly active reactor and novel ECL luminophore. On this basis, a novel co-quenching effect mechanism is proposed based on double-stranded DNA (dsDNA) triggered cooperation between LaMOFs and crystal violet (CV) molecules. Under the confined pore channels of LaMOFs, CV can play an important role as the photon-acceptor due to the matched absorption spectrum with the ECL spectrum of LaMOFs, and the electron-acceptor on account of its lowest unoccupied molecular orbital level. Based on the proposed co-quenching effect mechanism, a constructed ECL gene sensor shows good assay performance toward p53 gene in the detection range of 1 pm to 100 nm with a detection limit of 0.33 pm. The co-quenching effect integrating LaMOFs with CV is expected to be a versatile approach in the construction of ECL gene sensor, which has good prospect in expanding the application range of ECL technology.

Construction of Molecular Sensing and Logic Systems Based on Site-Occupying Effect-Modulated MOF-DNA Interaction.

Interactions between metal-organic frameworks (MOFs) and nucleic acids are of great importance in molecular assembly. However, current MOF-nucleic acid interactions lack diversity and are normally realized in an uncontrollable manner. Herein, the interaction of zirconium-based MOFs (Zr-MOFs) with nucleic acids is enabled by the formation of Zr-O-P bonds and further manipulated by a phosphate-induced site-occupying effect. Covering Zr ions in clusters of MOFs with phosphates impedes the formation of Zr-O-P bonds with nucleic acids, rendering the MOF-nucleic acid interaction tunable and stimulus-responsive. Notably, the experimental results demonstrate that various phosphates, Zr-MOFs, and nucleic acids can all be adopted in the tunable interaction. On the basis of these findings, fluorescent DNA and typical Zr-MOFs are proposed as functional probe-quencher pairs to establish molecular sensing and logic systems. Accordingly, alkaline phosphatase and inorganic pyrophosphatase can be quantified simultaneously, and the overall relation of different phosphates and phosphatases is facilely displayed. The work provides a general strategy for modulating MOF-nucleic acid interactions, which is conducive to the development of molecular intelligent systems.

Colloidal-sized zirconium porphyrin metal-organic frameworks with improved peroxidase-mimicking catalytic activity, stability and dispersity.

Metal-organic frameworks (MOFs) have attracted great attention as enzyme mimic materials in colorimetric hydrogen peroxide (H2O2) detection. At present, it is highly desirable but remains challenging to prepare MOFs with high stability and dispersity to further improve their peroxidase-mimicking catalytic activity. In this work, we developed a new and facile method for the synthesis of a sub-100 nm peroxidase-mimicking zirconium porphyrin metal-organic framework (Zr-PorMOF) via a solvothermal method. The experimental results indicated that compared with the micron-sized crystals obtained using a classical synthesis method, the catalytic activity, stability and dispersity in water of the colloidal Zr-PorMOF were obviously enhanced. The as-synthesized colloidal Zr-PorMOF was further successfully applied in colorimetric H2O2 detection, and satisfactory detection performance was obtained. Furthermore, the colloidal Zr-PorMOF was also successfully employed in the construction of a peroxidase-based tandem catalysis system. Taking glucose oxidase as an example, this system was successfully applied for glucose sensing in real human serum samples, which proved its practical feasibility in diabetes diagnosis and indicates its high potential feasibility in peroxidase-related applications in complex biomatrix.

Triple-Helix Molecular Switch Electrochemiluminescence Nanoamplifier Based on a S-Doped Lu2O3/Ag2S Pair for Sensitive MicroRNA Detection.

Development of sensitive detection methods for microRNAs has realistic application value for early clinical analysis and accurate diagnosis. In this study, a triple-helix molecular switch electrochemiluminescence resonance energy transfer (ECL-RET) nanoamplifier was designed to construct an electrochemiluminescence (ECL) biosensor for microRNA determination. The newly synthesized S-doped Lu2O3, which shows a 3 times better ECL performance than Lu2O3, was chosen as the donor in this ECL-RET system. Accordingly, Ag2S quantum dots (QDs) were used as the matched acceptor. They exhibited overlapping spectra and efficient energy transfer between each other. Furthermore, using a triple-helix switch structure with an improved quenching effect for signal amplification and a nano-DNA walker transformational system as a powerful method for target amplification, a supernanoamplifier was achieved. As a consequence, the proposed ECL biosensor for microRNA-141 detection exhibited good analytical performance with a low detection limit (16 aM). The sensor not only led to the development of a novel ECL-RET pair but also provided a strong nanoamplifier for biosensing platform construction, which may offer some new considerations regarding material design, signal amplification, and show promising application value in biomedical and clinical diagnosis.

Electrochemical Assay of the Alpha Fetoprotein-L3 Isoform Ratio To Improve the Diagnostic Accuracy of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is now the major malignant disease with high morbidity and mortality, which seriously endangers human lives and health. Alpha fetoprotein (AFP) assay is a commonly used serological biomarker for clinical diagnosis of HCC, but it lacks specificity. Analysis of its isoform AFP-L3, especially the AFP-L3 ratio in total AFP (AFP-L3%), can significantly improve the specificity for HCC identification. Herein, an electrochemical approach has been first proposed for simple, accurate, and fast determination of AFP-L3% in clinical samples. On the basis of two independent electrochemical signals generated from the synthesized nanoparticles, 4-mercaptophenylboronic acid (MPA)-functionalized copper nanoparticles (MPA-CuNPs) and the Lens culinaris agglutinin (LCA)-functionalized silver nanoparticles (LCA-AgNPs), simultaneous quantification of the AFP-L3 and total AFP in serum sample has been achieved, thus achieving directly the electrochemical assay of AFP-L3%. To be noted, both the assay time and the assay procedure have been significantly compressed when compared to that of available techniques in clinical use. Therefore, with the integration of electrochemical techniques, this new approach for AFP-L3% analysis would be promising for the accurate diagnosis of HCC.

Cucurbituril and Azide Cofunctionalized Graphene Oxide for Ultrasensitive Electro-Click Biosensing.

To achieve high selectivity and sensitivity simultaneously in an electrochemical biosensing platform, cucurbituril and azide cofunctionalized graphene oxide, a new functional nanomaterial that acts as a go-between to connect the recognition element with amplified signal architecture, is developed in this work. The cucurbituril and azide cofunctionalized graphene oxide features a high specific surface area with abundant levels of the two types of functional groups. Specifically, it emerges as a powerful tool to link recognition elements with simplicity, high yield, rapidity, and highly selective reactivity through azide-alkynyl click chemistry. Moreover, it possesses many host molecules to interact with guest molecules (also signal molecules)-grafted branched ethylene imine polymer, through which the detection sensitivity can be greatly improved. Together with electro-click technology, a highly controllable, selective, and sensitive biosensing platform can be easily created. For VEGF165 protein detection, the electro-click assay has high selectivity and sensitivity; a dynamic detection range from 10 fg mL-1 to 1 ng mL-1 with a detection limit of 8 fg mL-1 was achieved. The electro-click biosensing strategy based on cucurbituril and azide cofunctionalized graphene oxide would have great promise for other target analytes with a broad range of applications.

Aggregation of Individual Sensing Units for Signal Accumulation: Conversion of Liquid-Phase Colorimetric Assay into Enhanced Surface-Tethered Electrochemical Analysis.

A novel concept is proposed for converting liquid-phase colorimetric assay into enhanced surface-tethered electrochemical analysis, which is based on the analyte-induced formation of a network architecture of metal nanoparticles (MNs). In a proof-of-concept trial, thymine-functionalized silver nanoparticle (Ag-T) is designed as the sensing unit for Hg(2+) determination. Through a specific T-Hg(2+)-T coordination, the validation system based on functionalized sensing units not only can perform well in a colorimetric Hg(2+) assay, but also can be developed into a more sensitive and stable electrochemical Hg(2+) sensor. In electrochemical analysis, the simple principle of analyte-induced aggregation of MNs can be used as a dual signal amplification strategy for significantly improving the detection sensitivity. More importantly, those numerous and diverse colorimetric assays that rely on the target-induced aggregation of MNs can be augmented to satisfy the ambitious demands of sensitive analysis by converting them into electrochemical assays via this approach.

EvoVis: A Visual Analytics Method to Understand the Labeling Iterations in Data Programming.

Obtaining high-quality labeled training data poses a significant bottleneck in the domain of machine learning. Data programming has emerged as a new paradigm to address this issue by converting human knowledge into labeling functions(LFs) to quickly produce low-cost probabilistic labels. To ensure the quality of labeled data, data programmers commonly iterate LFs for many rounds until satisfactory performance is achieved. However, the challenge in understanding the labeling iterations stems from interpreting the intricate relationships between data programming elements, exacerbated by their many-to-many and directed characteristics, inconsistent formats, and the large scale of data typically involved in labeling tasks. These complexities may impede the evaluation of label quality, identification of areas for improvement, and the effective optimization of LFs for acquiring high-quality labeled data. In this paper, we introduce EvoVis, a visual analytics method for multi-class text labeling tasks. It seamlessly integrates relationship analysis and temporal overview to display contextual and historical information on a single screen, aiding in explaining the labeling iterations in data programming. We assessed its utility and effectiveness through case studies and user studies. The results indicate that EvoVis can effectively assist data programmers in understanding labeling iterations and improving the quality of labeled data, as evidenced by an increase of 0.16 in the average F1 score when compared to the default analysis tool.

Living electrochemical biosensing: Engineered electroactive bacteria for biosensor development and the emerging trends.

Bioelectrical interfaces made of living electroactive bacteria (EAB) provide a unique opportunity to bridge biotic and abiotic systems, enabling the reprogramming of electrochemical biosensing. To develop these biosensors, principles from synthetic biology and electrode materials are being combined to engineer EAB as dynamic and responsive transducers with emerging, programmable functionalities. This review discusses the bioengineering of EAB to design active sensing parts and electrically connective interfaces on electrodes, which can be applied to construct smart electrochemical biosensors. In detail, by revisiting the electron transfer mechanism of electroactive microorganisms, engineering strategies of EAB cells for biotargets recognition, sensing circuit construction, and electrical signal routing, engineered EAB have demonstrated impressive capabilities in designing active sensing elements and developing electrically conductive interfaces on electrodes. Thus, integration of engineered EAB into electrochemical biosensors presents a promising avenue for advancing bioelectronics research. These hybridized systems equipped with engineered EAB can promote the field of electrochemical biosensing, with applications in environmental monitoring, health monitoring, green manufacturing, and other analytical fields. Finally, this review considers the prospects and challenges of the development of EAB-based electrochemical biosensors, identifying potential future applications.

Experimental Investigation of CO2-Induced Silica Gel as the Water Blocking Grout Effect of Aquifer Ions.

This study aimed to prevent water flow in microcracks and simultaneously achieve CO2 capture during grouting (CCG). Using sodium silicate (SS) as the primary material, the microcracks were grouted by a two-step approach. The low-initial-viscosity (5 mPa s) SS was first saturated within the microcracks followed by CO2 injection at 2 MPa. Through CO2 dissolution, silica gel was developed and tolerated a hydraulic pressure of up to 5.5 MPa. The effects of aquifer ions (Na+, Ca2+, Mg2+, HCO3 -, and SO4 2-) were equally evaluated at harsh conditions, and it was found that the strength of the silica gel was reduced, which was caused by salting out, low CO2 solubility, and precipitation. As a result, the hydraulic pressure was reduced to as low as 3 MPa. After 210 days, 16% of the silica gels (without ion inclusion) were reversible to the liquid phase, where a similar effect was found in the cases of Na+ and Mg2+ ions. The degradation increased with more Ca2+ ions (up to 55%) and decreased with more HCO3 - and SO4 2- ions. Microcracks grouted with CCG extended the CO2 utilization in grouting application. Combined with the effect of dissolved ions, the proposed approach is feasible in the field implementation for underground engineering under water bodies.

Perspectives of metal-organic framework nanosystem to overcome tumor drug resistance.

Cancer is one of the most harmful diseases in the world, which causes huge numbers of deaths every year. Many drugs have been developed to treat tumors. However, drug resistance usually develops after a period of time, which greatly weakens the therapeutic effect. Tumor drug resistance is characterized by blocking the action of anticancer drugs, resisting apoptosis and DNA repair, and evading immune recognition. To tackle tumor drug resistance, many engineered drug delivery systems (DDS) have been developed. Metal-organic frameworks (MOFs) are one kind of emerging and promising nanocarriers for DDS with high surface area and abundant active sites that make the functionalization simpler and more efficient. These features enable MOFs to achieve advantages easily towards other materials. In this review, we highlight the main mechanisms of tumor drug resistance and the characteristics of MOFs. The applications and opportunities of MOF-based DDS to overcome tumor drug resistance are also discussed, shedding light on the future development of MOFs to address tumor drug resistance.

Nitrogen-doped carbons derived from cotton pulp for improved supercapacitors.

Supercapacitors have a rapid charge/discharge rate, long lifespan, high stability, and relatively acceptable cost, showing great potential in energy storage and conversion applications. However, the current cost-effective carbon-based electrodes have limited application owing to their low specific capacitance and unsatisfactory stability. In this regard, we herein prepare nitrogen-doped carbons by carbonizing a mixture of cotton pulp (CCP) and melamine to improve the specific capacitance by integrating pore (mesopore) and surface (oxygen-containing groups) modification with defect engineering via the carbonization process. Furthermore, the structural and morphological features of the resultant nitrogen-doped carbons are confirmed by various characterization techniques. Excitingly, the specific capacitance for nitrogen-doped CCP (CCPN1) with a 1 : 1 weight ratio of CCP and melamine is 642 F g-1 at a current density of 0.5 A g-1 in a three-electrode system, surpassing that of the reported carbon analogues and most metal-based materials to date. The stability test suggests that the specific capacitance of CCPN1 is maintained over 150 F g-1 at a current density of 2 A g-1 even over 5000 cycles. Therefore, the reported nitrogen-doped carbons from cotton pulp exhibit improved specific capacitance and stability, providing a new cost-effective carbon-based material for application in the energy storage field.

Direct acupuncture of nitric oxide by an electrochemical microsensor with high time-space resolution.

Measurement of signal molecule is critically important for understanding living systems. Nitric oxide (NO) is a key redox signal molecule that shows diverse roles in virtually all life forms. However, probing into NO's activities is challenging as NO has restricted lifetime (<10 s) and limited diffusion distance (usually <200 µm). So, for the direct acupuncture of NO within the time-space resolution, an electrochemical microsensor has been designed and fabricated in this work. Fabrication of the microsensor is achieved by (1) selective assembly of an electrocatalytic transducer, (2) attaching the transducer on carbon fiber electrode, and (3) covered it with a screen layer to reduce signal interference. The fabricated microsensor exhibits high sensitivity (LOD, 13.5 pM), wide detection range (100 pM-5 µM), and good selectivity. Moreover, studies have revealed that the availability of the sensor for efficient detection of NO is due to the formation of a specific DNA/porphyrin hybrid structure that has synergetic effects on NO electrocatalysis. Therefore, NO release by cells and tissues can be directly and precisely traced, in which we have obtained the release pattern of NO by different cancer cell lines, and have known its dynamics in tumor microenvironment. The fabricated electrocatalytic microsensor may provide a unique and useful tool for the direct assay of NO with high time-space resolution, which promisingly gives a technical solution for the bioassay of NO in living systems.

Enhanced electrochemiluminescence cytosensing based on abundant oxygen vacancies contained 2D nanosheets emitter coupled with DNA device cycle-amplification.

Developing efficient and sensitive cytosensing method has great significance for the detection of low abundant circulating tumor cells (CTCs). Electrochemiluminescence (ECL) biosensor, as an attractive analytical tool, has shown a great potential in sensitive cell counting. Its detection efficiency is strongly dependent on the electrochemiluminescent materials, whose property is related to its morphology and surface vacancies. Herein, the ultrathin Lu2O3-S nanosheets contain abundant oxygen vacancies were newly synthesized. Its special two-dimensional (2D) structure morphology and surface vacancy endowed it intensified and stable ECL emission. The possible mechanism was deduced from experiments and discussed. Then, through integrating with a DNA device cycle-amplification system plus signal conversion pretreatment, we constructed a crossed enhanced ECL cytosensing platform. In this system, the target cells were transformed into programmable sequences, which could be next coupled with DNA device cycle-amplification on the modified electrode surface. Using Ag2S quantum dots as the energy acceptor toward Lu2O3-S donor, and CCRF-CEM cells (CEM) as the model CTCs, an enhanced ECL cytosensing platform was proposed, displaying good analytical performance for acute lymphoblastic leukemia cancer cell detection. The ECL signal responded proportionately on the CEM cells concentration in a wide range of 5 × 10 to 1 × 106 cells/mL, and a low detection limit of 10 cells/mL was obtained. This work provided an alternative way to design high-performance ECL luminophores, and also would be an effective solution for CTCs counting.

A versatile switchable dual-modal colorimetric and photoelectrochemical biosensing strategy via light-controlled sway of a signal-output transverter.

A design criterion to construct a versatile dual-modal colorimetric and PEC biosensing platform for switching the corresponding mode freely is proposed via integration of a natural enzyme, light-activated nanozyme and light-controlled swayable signal-output transverter. A switchable dual-modal platform toward DNA analysis is developed as a proof of concept.