Locality Cross-domain Discriminant Analysis for Membranous Nephropathy Recognition using Microscopic Hyperspectral Imaging.

Cross-domain methods have been proposed to learn the domain invariant knowledge that can be transferred from the source domain to the target domain. Existing cross-domain methods attempt to minimize the distribution discrepancy of the domains. However, these methods fail to explore the domain invariant subspace due to the samples of different classes between two domains may overlap in the new subspace. They consider the features in the original space data that may be unnecessary or irrelevant to the final classification, and neglect to preserve the local manifold structure between two domains. To solve these problems, a novel feature extraction method called Locality Cross-domain Discriminant Analysis (LCDA) is proposed. LCDA first aligns the distributions and avoids overlap between two domains. Then, LCDA exploits the local manifold structure to maintain the discriminative capability of the low-dimensional projection matrices. Finally, a robust constraint is utilized to preserve the robustness of the projection matrices. The proposed LCDA not only avoids overlap between different classes but also explores the local manifold information. Experiment results on the medical membranous nephropathy hyperspectral dataset demonstrate that the proposed LCDA has better performance than other relevant feature extraction methods.

Design and Analysis Method of Piezoelectric Liquid Driving Device with Elastic External Displacement.

In piezoelectric drive, resonant drive is an important driving mode in which the external elastic force and electric drive signal are the key factors. In this paper, the effects of the coupling of external elastic force and liquid parameters with the structure on the vibrator resonance frequency and liquid drive are analyzed by numerical simulation. The fluid-structure coupling model for numerical analysis of the elastic force was established, the principle of microdroplet generation and the coupling method of the elastic force were studied, and the changes in the resonant frequency and mode induced by the changes in the liquid parameters in different cavities were analyzed. Through the coupled simulation and calculation of the pressure and deformation of the cavity, the laser vibration measurement test was carried out to test the effect of the vibration mode analysis. The driving model of the fluid jet driven by the elastic force on the piezoelectric drive was further established. The changing shape of the fluid jet under different elastic forces was analyzed, and the influence law of the external elastic force on the change in the droplet separation was determined. It provides reference support for further external microcontrol of droplet motion.

Fully integrated on-chip FBG interrogator for high-accuracy measurement of wavelengths.

We present the design and fabrication of an on-chip FBG interrogator based on arrayed waveguide grating (AWG) technology. The spectral overlap between adjacent channels in the integrated AWG is significantly enhanced through a combination approach involving the reduction of the output waveguide spacing and an increase in the input waveguide width. As a result of these design choices, our AWG demonstrates excellent spectral consistency, with spectral cross talk exceeding 30 dB. The interrogator seamlessly combining optical and circuitry components achieves full integration and enables a wide range of interrogation wavelengths, including C-band and L-band. With an interrogation range extending up to 80 nm, it theoretically has the capacity to simultaneously interrogate the wavelengths of 20 FBG sensors. Experimental findings demonstrate an absolute interrogation accuracy of less than 2 pm for the fully integrated interrogator. With its compact size, cost-effectiveness, exceptional precision, and ease of integration, the proposed interrogator holds a substantial promise for widespread application in the realm of FBG sensing.

Bifunctional electrochemical biosensor based on PB-MXene films for the real-time analysis and detection of living cancer cells.

Circulating tumor cells (CTCs) are important prognostic markers for cancer diagnosis and metastasis, and their detection is an important means to detect cancer metastasis. Herein, we construct a novel bifunctional electrochemical biosensor based on the PB-MXene composite films. A simple electrostatic self-assembly approach was employed to prepare a film composed of PB nanocubes on the MXene substrates. Given that the PB is an artificial peroxidase for H2O2 sensing, the PB-MXene films can realize the real-time monitoring of H2O2 secretion from living CTCs. Besides, the anti-CEA attached biosensors can be utilized to quantify the corresponding CTCs. The synergic effects of the MXene with a large specific area and PB with enzyme-free catalysis for H2O2 resulted in PB-MXene films exhibiting high electrocatalytic and low cytotoxicity for both H2O2 sensing and living CTCs capturing. As a result, the biosensor shows a low detection limit of 0.57 µM towards H2O2 with a wide linear range (1 µM to 500 µM), as well as an excellent sensing performance for CTCs (an extremely low detection limit of 9 cells/mL in a wide linear range of 1.3 ×101 to 1.3 ×106 cells/mL). Moreover, the prepared biosensor showed satisfactory stability and anti-interference ability for potential applications in clinical cancer diagnosis and tumor metastasis.

Hierarchical finite-time cooperative control for teleoperation of networked disturbed mobile manipulators.

This paper investigates the teleoperation problem of networked disturbed mobile manipulators (NDMMs), in which the human operator remotely controls multiple slave mobile manipulators through a master manipulator. Each individual of the slave ones consisted of a nonholonomic mobile platform and a holonomic constrained manipulator that is mounted on the nonholonomic mobile platform. The cooperative control objective of the considered teleoperation problem includes: (1) synchronizing the states of the slave manipulators to the human-controlled master one; (2) forcing the mobile platforms of the slave ones to form a user-defined formation; (3) controlling the geometric center of all the platforms to track a reference trajectory. We present a hierarchical finite-time cooperative control (HFTCC) framework to achieve the cooperative control goal in a finite time. The presented framework includes the distributed estimator, the weight regulator and the adaptive local controller, where the estimator generates the estimated states of the desired formation and trajectory, the regulator selects the slave robot that the master one needs to track, as well as the presented adaptive local controller guarantees the finite-time convergence of the controlled states with model uncertainties and disturbances. Additionally, for improving the telepresence, a novel super twisting observer is presented to reconstruct the interaction force between the salve mobile manipulators and the remote operating environment on the master (i.e., the human) side. Finally, the effectiveness of the proposed control framework is demonstrated by several simulation results.

High-Performance Detection of Exosomes Based on Synergistic Amplification of Amino-Functionalized Fe3O4 Nanoparticles and Two-Dimensional MXene Nanosheets.

Exosomes derived from cancer cells have been recognized as a promising biomarker for minimally invasive liquid biopsy. Herein, a novel sandwich-type biosensor was fabricated for highly sensitive detection of exosomes. Amino-functionalized Fe3O4 nanoparticles were synthesized as a sensing interface with a large surface area and rapid enrichment capacity, while two-dimensional MXene nanosheets were used as signal amplifiers with excellent electrical properties. Specifically, CD63 aptamer attached Fe3O4 nanoprobes capture the target exosomes. MXene nanosheets modified with epithelial cell adhesion molecule (EpCAM) aptamer were tethered on the electrode surface to enhance the quantification of exosomes captured with the detection of remaining protein sites. With such a design, the proposed biosensor showed a wide linear range from 102 particles µL-1 to 107 particles µL-1 for sensing 4T1 exosomes, with a low detection limit of 43 particles µL-1. In addition, this sensing platform can determine four different tumor cell types (4T1, Hela, HepG2, and A549) using surface proteins corresponding to aptamers 1 and 2 (CD63 and EpCAM) and showcases good specificity in serum samples. These preliminary results demonstrate the feasibility of establishing a sensitive, accurate, and inexpensive electrochemical sensor for detecting exosome concentrations and species. Moreover, they provide a significant reference for exosome applications in clinical settings, such as liquid biopsy and early cancer diagnosis.

FSG-based divinable time-varying formation tracking of multiple Lagrangian agents with unknown disturbances and directed graphs.

In this paper, a flexible shape generator (FSG) is designed to achieve the divinable transformation process of the time-varying formation, and consider the FSG-based time-varying formation tracking (TVFT) problem of multiple Lagrangian agents with unknown disturbances and directed graphs. A hierarchical control algorithm is newly designed to achieve the control goal without using the prior information of the system model and bounded disturbances, and the specific implementation of the proposed hierarchical algorithms is also provided. By using the Hurwitz criterion and adaptive system theory, the sufficient conditions are derived and the stability analysis show that the formation tracking errors of the considered system are uniform ultimate bounded. Several simulation examples are performed on five two-degree-of-freedom mechanical arms to show the effectiveness of theoretical results.

Nitrogen-doped cyan-emissive carbon quantum dots for fluorescence tetracycline detection and lysosome imaging.

Tetracyclines (TCs) prevent the growth of peptide chains and the synthesis of proteins, and they are widely used to inhibit Gram-positive and -negative bacteria. For the detection of tetracyclines in cell and in vitro, a convenient and simple detection system based on nitrogen-doped cyan carbon quantum dots (C-CQDs) was developed. C-CQDs have excellent excitation-independent properties, the best optimal excitation peak is 360 nm and the best emission peak is 480 nm. Based on the inner filter effect (IFE), the fluorescence intensity of C-CQDs in solution decreases with the increase of tetracyclines. In the range of 0-100 µM, C-CQDs present a good linear relationship with three tetracyclines (CTC, TET, OCT), with R 2 all greater than 0.999. C-CQDs can detect tetracycline in milk samples with recovery in the range of 98.2-103.6%, which demonstrates their potential and broad application in real samples. Furthermore, C-CQDs exhibit excellent lysosomal targeting, as indicated by a Pearson's coefficient of 0.914 and an overlap of 0.985. The internalisation of C-CQDs was mainly affected by lipid raft-mediated endocytosis in endocytic pathway experiments. These experiments indicate that C-CQDs can be effectively used to detect TC content and target lysosomes as an alternative to commercial dyes.

Hierarchical Au nanoarrays functionalized 2D Ti2CTx MXene membranes for the detection of exosomes isolated from human lung carcinoma cells.

Exosome is considered an important biomarker of liquid biopsy in early cancer screening, which can reflect the physiological and pathological status of cancer cells. Herein, we construct a novel electrochemical biosensor based on hierarchical Au nanoarray-modified 2D Ti2CTx MXene membranes for sensitive detection of exosomes. Ti2CTx MXene nanosheets were fabricated as the building blocks for preparing 2D membranes as the sensing platform via vacuum filtration. To enhance the conductivity of the MXene membrane, for the first time, hierarchical Au nanoarrays were further deposited in situ on the MXene membrane surface. The combination of MXene membrane with a large specific area and hierarchical Au nanoarrays with excellent conductivity make higher electrocatalytic and more active sites in aptamer immobilization. In this strategy, the composite membrane modified by EpCAM recognized aptamer can specifically capture target exosomes, meanwhile, these target exosomes anchor aptamer for CD63 to further enhance the sensing sensitivity and accuracy of the biosensor. As a result, the biosensor achieved high sensitivity and reliable performance for exosome sensing, with a low detection limit (58 particles/µL) in the linear range of 1 × 102 to 1 × 107 particles/µL. In addition, this biosensor showed satisfactory electrochemical stability and anti-interference ability for the detection of exosomes in real serum samples.

Design, Synthesis, and Application of Carbon Dots With Synergistic Antibacterial Activity.

The diversity of bacteria and their ability to acquire drug resistance lead to many challenges in traditional antibacterial methods. Photothermal therapies that convert light energy into localized physical heat to kill target microorganisms do not induce resistance and provide an alternative for antibacterial treatment. However, many photothermal materials cannot specifically target bacteria, which can lead to thermal damage to normal tissues, thus seriously affecting their biological applications. Here, we designed and synthesized bacteria-affinitive photothermal carbon dots (BAPTCDs) targeting MurD ligase that catalyzes the synthesis of peptidoglycan (PG) in bacteria. BAPTCDs presented specific recognition ability and excellent photothermal properties. BAPTCDs can bind to bacteria very tightly due to their chiral structure and inhibit enzyme activity by competing with D-glutamic acid to bind to MurD ligases, thus inhibiting the synthesis of bacterial walls. It also improves the accuracy of bacteria treatment by laser irradiation. Through the synergy of biochemical and physical effects, the material offers outstanding antibacterial effects and potentially contributes to tackling the spread of antibiotic resistance and facilitation of antibiotic stewardship.

Ultra-bright carbon quantum dots for rapid cell staining.

Cellular imaging using carbon dots is an important research method in several fields. Herein, green-emissive carbon quantum dots (G-CDs) with a pretty high absolute quantum yield (QY) were fabricated via a one-step solvothermal method by using m-phenylenediamine and concentrated hydrochloric acid. G-CDs displayed strong green fluorescence with excitation/emission peaks at 460/500 nm, and their absolute quantum yield was as high as 58.65%. Further experiments suggested that the G-CDs we prepared have good solubility, excellent biocompatibility, and the capacity of rapidly imaging HeLa and 4T1 cells. Over expectations, the G-CDs could penetrate cells in only 10 s and the confocal images showed that the G-CDs could target the nucleus of cells. Moreover, by using 920 nm as the excitation wavelength, two-photon imaging has been successfully applied to 4T1 cells, overcoming the inherent limitations of single-photon imaging. The extremely high absolute quantum efficiency, ultra-fast imaging speed, and two-photon imaging capability make the G-CDs have good application potential in biomedical analysis and the clinical diagnostic field.

Biomimetic Redox-Responsive Mesoporous Organosilica Nanoparticles Enhance Cisplatin-Based Chemotherapy.

Cisplatin-based chemotherapy is dominated in several cancers; however, insufficient therapeutic outcomes and systemic toxicity hamper their clinical applications. Controlled release of cisplatin and reducing inactivation remains an urgent challenge to overcome. Herein, diselenide-bridged mesoporous organosilica nanoparticles (MON) coated with biomimetic cancer cell membrane were tailored for coordination responsive controlled cisplatin delivery and GSH depletion to strengthen Pt-based chemotherapy. Cisplatin-loaded MON (MON-Pt) showed high loading capacity due to robust coordination between selenium and platinum atoms and preventing premature leakage in normal tissue. MON-Pt exhibited a controlled release of activated cisplatin in response to the redox tumor microenvironment. Meanwhile, MON-Pt containing redox-responsive diselenide bonds could efficiently scavenge intracellular inactivation agents, such as GSH, to enhance Pt-based chemotherapy. 4T1 breast cancer cell membranes cloaked MON-Pt (MON-Pt@CM) performed efficient anticancer performance and low in vivo system toxicity due to long blood circulation time and high tumor accumulation benefiting from the tumor targeting and immune-invasion properties of the homologic cancer cell membrane. These results suggest a biomimetic nanocarrier to control release and reduce the inactivation of cisplatin for efficient and safe Pt-based chemotherapy by responding and regulating the tumor microenvironment.

A light-driven dual-nanotransformer with deep tumor penetration for efficient chemo-immunotherapy.

Designing a transformable nanosystem with improved tumor accumulation and penetration by tuning multiple physicochemical properties remains a challenge. Here, a near-infrared (NIR) light-driven nanosystem with size and charge dual-transformation for deep tumor penetration is developed. Methods: The core-shell nanotransformer is realized by integrating diselenide-bridged mesoporous organosilica nanoparticles as a reactive oxygen species (ROS)-responsive core with an indocyanine green (ICG)-hybrid N-isopropyl acrylamide layer as a thermosensitive shell. After loading doxorubicin (DOX), negatively charged nanomedicine prevents DOX leakage, rendering prolonged blood circulation time and high tumor accumulation. Results: Upon NIR light irradiation, mild photothermal effects facilitate the dissociation of the thermosensitive shell to achieve negative-to-positive charge reversal. Meanwhile, ICG-generated ROS cleave the diselenide bond of the organosilica core, resulting in rapid matrix degradation that produces DOX-containing smaller fragments. Such a light-driven dual-transformable nanomedicine simultaneously promotes deep tumor penetration and implements sufficient chemotherapy, along with evoking robust immunogenic cell death effects in vitro and in vivo. With the combination of a programmed cell death protein-1 (PD-1) checkpoint blockade, the nanotransformer remarkably blocks primary tumor growth and pulmonary metastasis of breast cancer with low systemic toxicity. Conclusions: This study develops a promising strategy to realize high tumor accumulation and deep penetration of light-transformable nanomedicine for efficient and safe chemo-immunotherapy.

Event-Triggered Consensus Control for Networked Underactuated Robotic Systems.

In this article, the consensus of networked underactuated robotic systems subject to fixed and switched communication networks is discussed by developing some novel event-triggered control algorithms, which can synchronously guarantee the convergence of the active states, the boundedness of the velocities of passive actuators, and the exclusion of Zeno behaviors. In the cases of fixed networks, the sufficient criteria are established for the presented distributed event-triggered mechanisms with and without using neighbors' velocities, in order to achieve a better tradeoff between the communication load and system performance. Besides, in the situation of switched networks, the sufficient criterion is established by assuming that the union of the network has a spanning tree. A distributed sampled-data rule is constructed to decide when to update its own and neighbors' estimated positions, and thus further reduces the unnecessary control cost. Finally, by further extending the main results to three other sampled-data control algorithms, several examples with performance comparisons are provided to validate the efficiency and advantages of the theoretical results.

Lag-Bipartite Formation Tracking of Networked Robotic Systems Over Directed Matrix-Weighted Signed Graphs.

This article studies the lag-bipartite formation tracking (LBFT) problem of the networked robotic systems (NRSs) with directed matrix-weighted signed graphs. Unlike the traditional formation tracking problems with only cooperative interactions, solving the LBFT problem implies that: 1) the robots of the NRS are divided into two complementary subgroups according to the signed graph, describing the coexistence of cooperative and antagonistic interactions; 2) the states of each subgroup form a desired geometric pattern asymptotically in the local coordinate; and 3) the geometric center of each subgroup is forced to track the same leader trajectory with different plus-minus signs and a time lag. A new hierarchical control algorithm is designed to address this challenging problem. Based on the Lyapunov stability argument and the property of the matrix-weighted Laplacian, some sufficient criteria are derived for solving the LBFT problem. Finally, simulation examples are proposed to validate the effectiveness of the main results.

Multifunctional Gold Nano-Cytosensor With Quick Capture, Electrochemical Detection, and Non-Invasive Release of Circulating Tumor Cells for Early Cancer Treatment.

Circulating tumor cells (CTCs) are metastatic tumor cells that shed into the blood from solid primary tumors, and their existence significantly increases the risk of metastasis and recurrence. The timely discovery and detection of CTCs are of considerable importance for the early diagnosis and treatment of metastasis. However, the low number of CTCs hinders their detection. In the present study, an ultrasensitive electrochemical cytosensor for specific capture, quantitative detection, and noninvasive release of EpCAM-positive tumor cells was developed. The biosensor was manufactured using gold nanoparticles (AuNPs) to modify the electrode. Three types of AuNPs with controllable sizes and conjugated with a targeting molecule of monoclonal anti-EpCAM antibody were used in this study. Electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) of the cytosensors were performed to evaluate the cell capture efficiency and performance. The captured 4T1 cells by the AuNPs hindered electron transport efficiency, resulting in increased EIS responses. The cell capture response recorded using EIS or DPV indicated that the optimal AuNPs size should be 17 nm. The cell capture response changed linearly with the concentration range from 8.0 × 10 to 1 × 107 cells/mL, and the limit of detection was 50 cells/mL. After these measurements, glycine-HCl (Gly-HCl) was used as an antibody eluent to destroy the binding between antigen and antibody to release the captured tumor cells without compromising their viability for further clinical research. This protocol realizes rapid detection of CTCs with good stability, acceptable assay precision, significant fabrication reproducibility with a relative standard deviation of 2.09%, and good recovery of cells. Our results indicate that the proposed biosensor is promising for the early monitoring of CTCs and may help customize personalized treatment options.

Specific recognition and photothermal release of circulating tumor cells using near-infrared light-responsive 2D MXene nanosheets@hydrogel membranes.

2D materials with attractive optical properties are promising for individualized cancer immunotherapy. Isolation, capture, and release of circulating tumor cells (CTCs) are of great significance for promoting the process of early diagnosis of cancers. MXene nanosheets incorporated gelatin hydrogel offers the possibility of achieving near-infrared (NIR) light response to initiate the photothermal effect. Herein, the design and preparation of Ti3C2Tx MXene nanosheets-embedded thermoresponsive gelatin hydrogel membrane with NIR light-responsive for the specific capture and release of CTCs were reported. The membrane was fabricated by casting Ti3C2Tx-embedded gelatin onto a substrate and then modified with epithelial-cell adhesion-molecule antibody (anti-EpCAM) for the specific recognition and separation of CTCs from whole blood. The captured cells can be released without damage with dual-mode containing temperature-responsive release (gelatin deconstructed at 37 °C) and photothermal site-release (Ti3C2Tx induced by NIR light). Furthermore, we were able to achieve an average efficient release rate of 89 % of captured cells with stable cell viability of 87 % via the NIR light irradiation. This work may provide the promising potential for retrieval of single cells in clinical diagnosis.

Iron and nitrogen-co-doped carbon quantum dots for the sensitive and selective detection of hematin and ferric ions and cell imaging.

Iron, nitrogen-co-doped carbon quantum dots (Fe,N-CDs) were prepared via a simple one-step hydrothermal method. The quantum yield of fluorescence reached about 27.6% and the blue-emissive Fe,N-CDs had a mean size of 3.76 nm. The as-prepared carbon quantum dots showed good solubility, a high quantum yield, good biocompatibility, low cytotoxicity, and high photostability. Interestingly, the as-prepared Fe,N-CDs exhibited good selectivity and sensitivity toward both hematin and ferric ions, and the limit of detection for hematin and ferric ions was calculated to be about 0.024 µM and 0.64 µM, respectively. At the same time, Fe,N-CDs were used for imaging HeLa cells and showed that most Fe,N-CDs were detained in the lysosome. Thus, this fluorescent probe has potential application in the quantitative detection of hematin or Fe3+ in a complex environment and for determining Fe3+ at the cellular level.

Coordination and Redox Dual-Responsive Mesoporous Organosilica Nanoparticles Amplify Immunogenic Cell Death for Cancer Chemoimmunotherapy.

Amplifying the chemotherapy-driven immunogenic cell death (ICD) for efficient and safe cancer chemoimmunotherapy remains a challenge. Here, a potential ICD nanoamplifier containing diselenide-bridged mesoporous organosilica nanoparticles (MONs) and chemotherapeutic ruthenium compound (KP1339) to achieve cancer chemoimmunotherapy is tailored. KP1339-loaded MONs show controlled drug release profiles via glutathione (GSH)-responsive competitive coordination and matrix degradation. High concentration of MONs selectively evoked reactive oxygen species production, GSH depletion, and endoplasmic reticulum stress in cancer cells, thus amplifying the ICD of KP1339 and boosting robust antitumor immunological responses. After the combination of PD-L1 checkpoint blockade, cancer cell membrane-cloaked KP1339-loaded MONs not only regress primary tumor growth with low systemic toxicity, but also inhibit distant tumor growth and pulmonary metastasis of breast cancer. The results have shown the potential of coordination and redox dual-responsive MONs boosting amplified ICD for cancer chemoimmunotherapy.

Simultaneous Recognition of Dopamine and Uric Acid in the Presence of Ascorbic Acid via an Intercalated MXene/PPy Nanocomposite.

Two-dimensional (2D) MXenes have shown a great potential for chemical sensing due to their electric properties. In this work, a Ti3C2Tx/polypyrrole (MXene/PPy) nanocomposite has been synthesized and immobilized into a glassy carbon electrode to enable the simultaneous recognition of dopamine (DA) and uric acid (UA) under the interference of ascorbic acid (AA). The multilayer Ti3C2Tx MXene was prepared via the aqueous acid etching method and delaminated to a single layer nanosheet, benefiting the in-situ growth of PPy nanowires. The controllable preparation strategy and the compounding of PPy material remain great challenges for further practical application. A facile chemical oxidation method was proposed to regulate magnitude and density during the forming process of PPy nanowire, which promotes the conductivity and the electrochemical active site of this as-prepared nanomaterial. The MXene/PPy nanocomposite-modified electrode exhibited the selective determination of DA and UA in the presence of a high concentration of AA, as well as a wide linear range (DA: 12.5-125 µM, UA: 50-500 µM) and a low detection limit (DA: 0.37 µM, UA: 0.15 µM). More importantly, the simultaneous sensing for the co-existence of DA and UA was successfully achieved via the as-prepared sensor.