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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Dual-path modulation of hydrogen peroxide to ameliorate hypoxia for enhancing photodynamic/starvation synergistic therapy.

The common existence of hypoxia within the tumor microenvironment severely restricts the efficacy of photodynamic therapy (PDT), which is attributed to the fact that the PDT process is strongly oxygen (O2) dependent. Here, a multifunctional composite (named CPCG), which combines polyethylene glycol (PEG) functionalized cerium oxide nanoparticles (CeO2) with photosensitizer chlorin e6 (Ce6) and glucose oxidase (GOx), is reported for generating O2 within the tumor microenvironment by the dual-path hydrogen peroxide (H2O2)-modulated ways to ameliorate hypoxia, thereby enhancing the PDT efficiency. This process is realized based on the dual enzyme-like activity of CeO2. The first modulated way is to transform the superoxide anion (O2˙-) into H2O2 by the superoxide dismutase-like activity of CeO2. The second modulated way is to decompose glucose into H2O2 through the catalysis of GOx. Subsequently, H2O2 generated from the above dual modulated ways can further produce O2via the catalase-like activity of CeO2. Additionally, the depletion of glucose could impede the nutrient supply to obtain starvation therapy. Both in vitro and in vivo experiments indicate that the CPCG composite could enhance the efficacy of photodynamic/starvation synergistic therapy. Therefore, this strategy offers great potential to modulate the O2 level in the tumor microenvironment for better therapeutic outcomes, and can act as a promising candidate in photodynamic/starvation synergistic therapy.

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.

Photo-affinity pulling down of low-affinity binding proteins mediated by post-translational modifications.

Weak and transient protein-protein interactions (PPIs) mediated by the post-translational modifications (PTMs) play key roles in biological systems. However, technical challenges to investigate the PTM-mediated PPIs have impeded many research advances. In this work, we develop a photo-affinity pull-down assay method to pull-down low-affinity binding proteins, thus for the screen of PTM-mediated PPIs. In this method, the PTM-mediated non-covalent interactions can be converted to the covalent interactions by the photo-activated linkage, so as to freeze frame the low-affinity binding interactions. The fabricated photo-affinity magnetic beads (PAMBs) ensure high specificity and resolution to capture the interacted proteins. Besides, the introduction of PEG passivation layer on PAMB has significantly reduced the non-specific interaction as compared to the traditional pull-down assay. For proof-of-concept, by using this newly developed assay method, we have identified a set of proteins that can interact with a specific methylation site on Flap Endonuclease 1 (FEN1) protein. Less interfering proteins (decreased over 80%) and more proteins sub-classes are profiled as compared to the traditional biotin-avidin pull-down system. Therefore, this new pull-down method may provide a useful tool for the study of low-affinity PPIs, and contribute to the discovery of potential targets for renewed PTM-mediated interactions that is fundamentally needed in biomedical research.

Highly sensitive and selective colorimetric sensor for thiocyanate based on electrochemical oxidation-assisted complexation reaction with Gold nanostars etching.

In this work, we developed an electrochemical oxidation-assisted complexation strategy for highly sensitive and selective detection of thiocyanate (SCN-). Gold nanostars (AuNSs) with uniform and sharp tips were first prepared, and we found they can be quickly etched to gold nanoparticles (AuNPs) under electrochemical oxidation with the existence of halide and halogen-like ions. Through introducing SCN--selective molecule: zinc phthalocyanine (ZnPc), the fabricated ZnPc-AuNSs/ITO electrode can rapidly and selectively response to SCN- under electrochemical oxidation, manifesting as a noticeable change in color from navy blue to red. Thus SCN- concentration can be easily reflected. The wide wavelength tuning range of AuNSs to AuNPs make the ZnPc-AuNSs/ITO sensor obtain a much wider detection range for SCN- (10 nM to 80 mM) than most other reported studies. In addition, the detection limit is as low as 3 nM. It renders the sensor to be easily used in much diluted matrixes, which can further lower the interference. We further applied the colorimetric sensor to SCN- detection in wastewater and milk, excellent performance was obtained. The proposed electrochemical oxidation-assisted complexation strategy will have good promise in developing colorimetric sensors with high selectivity and wide detection range, and will display more useful application in environmental monitoring.

Bovine serum albumin encapsulation of near infrared fluorescent nano-probe with low nonspecificity and cytotoxicity for imaging of HER2-positive breast cancer cells.

Breast cancer with HER2 overexpressing type links to malignant tumor growth and poor clinical outcome. Successful development of sensitive and selective nano-probe for identification of HER2-positive breast cancer cells is of great importance for breast cancer early diagnosis, subtype classification, and treatment planning. Herein, we report a HER2 antibody conjugated near infrared (NIR) emitted MnCuInS/ZnS qumtun dots (QDs) encapsulated bovine serum albumin (BSA) nano-probe for accurately targeted imaging of HER2-positive breast cancer cells. This NIR nano-probe shows good biocompatibility, low nonspecificity and cytotoxicity, high colloidal stability, and allows HER2-positive breast cancer cell identification with good selectivity. The practicality of this targeted NIR fluorescent nano-probe was proved by successful identifying HER2-positive breast cancer cells from HER2-negative breast cancer cells, which indicates that it can be efficiently applied in selective screening of HER2 overexpressing cancer cells, and provide a platform for the strategy design on the distinction of different breast cancer subtypes.