Marriage of a Dual-Plasmonic Interface and Optical Microfiber for NIR-II Cancer Theranostics.

The use of light as a powerful tool for disease treatment has introduced a new era in tumor treatment and provided abundant opportunities for light-based tumor theranostics. This work reports a photothermal theranostic fiber integrating cancer detection and therapeutic functions. Its self-heating effect can be tuned at ultralow powers and used for self-heating detection and tumor ablation. The fiber, consisting of a dual-plasmonic nanointerface and an optical microfiber, can be used to distinguish cancer cells from normal cells, quantify cancer cells, perform hyperthermal ablation of cancer cells, and evaluate the ablation efficacy. Its cancer cell ablation rate reaches 89% in a single treatment. In vitro and in vivo studies reveal quick, deep-tissue photonic hyperthermia in the NIR-II window, which can markedly ablate tumors. The marriage of a dual-plasmonic nanointerface and an optical microfiber presents a novel paradigm in photothermal therapy, offering the potential to surmount the challenges posed by limited light penetration depth, nonspecific accumulation in normal tissues, and inadvertent damage in current methods. This work thus provides insight for the exploration of an integrated theranostic platform with simultaneous functions in cancer diagnostics, therapeutics, and postoperative monitoring for future practical applications.

Optical Microfiber with a Gold Nanorods-Black Phosphorous Nanointerface: An Ultrasensitive Biosensor and Nanotherapy Platform.

The detection and therapy of cancers in the early stage significantly alleviate the associated dangers. Optical devices offer new opportunities for these early measures. However, the clinical translation of the existing methods is severely hindered by their relatively low sensitivity or unclear physiological metabolism. Here, an optical microfiber sensor with a drug loading gold nanorod-black phosphorous nanointerface, as an ultrasensitive biosensor and nanotherapy platform, is developed to meet the early-stage requirement. With interface sensitization and functionalization of the hybrid nanointerface, the microfiber sensor presents an ultrahigh sensing performance, achieving the selective detection of the HER2 biomarker with limits of detection of 0.66 aM in buffer solution and 0.77 aM in 10% serum. It can also distinguish breast cancer cells from other cells in the early stage. Additionally, enabled by the interface, the optical microfiber is able to realize cellular nanotherapy, including photothermal/chemotherapy with pump laser coupling after diagnosis, and evaluate therapy results in real time. The immobilization of the interface on the optical microfiber surface prevents the damage to normal cells induced by nanomaterial enrichment, making the device more efficient and intelligent. This study opens up a new avenue for the development of smart optical platforms for sensitive biosensing and precision therapy.

Insights into the mechanisms of Th17 differentiation and the Yin-Yang of Th17 cells in human diseases.

Th17 cells are a lineage of CD4+ T helper cells with Th17-specific transcription factors RORγt and RoRα. Since its discovery in 2005, research on Th17 has been in rapid progress, and increasing cytokines or transcription factors have been uncovered in the activation and differentiation of Th17 cells. Furthermore, growing evidence proves there are two different subsets of Th17 cells, namely non-pathogenic Th17 (non-pTh17) and pathogenic Th17 (pTh17), both of which play important roles in adaptive immunity, especially in host defenses, autoimmune diseases, and cancer. In this review, we summarize and discuss the mechanisms of Th17 cells differentiation, and their roles in immunity and diseases.

Co-delivery of Doxorubicin and Curcumin with Polypeptide Nanocarrier for Synergistic Lymphoma Therapy.

The traditional chemotherapy, including Adriamycin (Doxorubicin, DOX), is widely used and is part of the first-line chemotherapy of invasive B cell lymphoma. DOX is nonselective cytotoxic drug and has many adverse effects, which limit its clinical application in combination with other anti-cancer drugs. Optimization of the delivery system targeting tumor microenvironment could be a feasible approach that may have significant clinical significance. Further, combination of DOX with other anticancer drugs, such as curcumin, can enhance the synergistic effects, possibly through epigenetic mechanisms. Hence, we evaluated the efficacy and toxicity of novel nanoparticles that enable the co-delivery of DOX and curcumin in the treatment of invasive B cell lymphoma both in vivo and vitro. The polymer nano materials [mPEG-b-P(Glu-co-Phe)] was used to co-load DOX and curcumin (CUR): L-DOX + CUR. DOX signal was measured to determine the ability of the drugs entering the cells by flow cytometry, and the different enrichment areas in the cells were directly observed by confocal microscope. The toxicity of LDOX + CUR was tested by CCK-8 assay in different cells, and the synergistic coefficients were calculated. The cell apoptosis and the possible mechanisms of apoptosis pathways regulation by L-DOX + CUR were examined using flow cytometry and Western Blot. The MTD (maximum tolerable dose) test was performed in mice. Tumor-bearing SCID mice (i.e., BJAB cell) were used to evaluate the in vivo efficacy of L-DOX + CUR. L-DOX + CUR, was prepared successfully, and the mole ratio of DOX and CUR fixed in 1.0:1.2. (DOX loading rate 9.7%, CUR loading rate 8.1%). L-DOX + CUR exhibited increased intracellular delivery and the main enrichment area of DOX was nucleus. L-DOX + CUR increased cytotoxicity, induced higher rates of apoptosis, and had synergistic effect, especially in BJAB cells (min CI 0.019). It even had epigenetic effect and affected miRNA levels favorably by down-regulating miR-21, miR-199a and up-regulating miR-98 and miR-200c. Additionally, L-DOX + CUR increased MTD in Kunming mice (i.e., 25 mg/kg), compared to DOX (10 mg/kg) and L-DOX (20 mg/kg). In BJAB cell bearing SCID mice, L-DOX + CUR treatment suppressed tumor growth compared to DOX or L-DOX alone, and exhibited less weight loss in mice. We developed new polymer nanoparticles-mPEG-b-P (Glu-co-Phe) co-loaded with DOX and DUR. L-DOX + CUR exhibited synergistic cytotoxic and apoptotic effects on invasive B cell lymphoma. Treatment of L-DOX + CUR potentiated tumor killing in xenografts and reduced toxicity in vivo.

Happy emotion cognition of bimodal audiovisual stimuli optimizes the performance of the P300 speller.

OBJECTIVE: Prior studies of emotional cognition have found that emotion-based bimodal face and voice stimuli can elicit larger event-related potential (ERP) amplitudes and enhance neural responses compared with visual-only emotional face stimuli. Recent studies on brain-computer interface have shown that emotional face stimuli have significantly improved the performance of the traditional P300 speller system, but its performance needs to be further improved for practical applications. Therefore, we herein propose a novel audiovisual P300 speller based on bimodal emotional cognition to further improve the performance of the P300 system. METHODS: The audiovisual P300 speller we proposed is based on happy emotions, with visual and auditory stimuli that consist of several pairs of smiling faces and audible chuckles (E-AV spelling paradigm) of different ages and sexes. The control paradigm was the visual-only emotional face P300 speller (E-V spelling paradigm). RESULTS: We compared the ERP amplitudes, accuracy, and raw bit rate between the E-AV and E-V spelling paradigms. The target stimuli elicited significantly increased P300 amplitudes (p < .05) and P600 amplitudes (p < .05) in the E-AV spelling paradigm compared with those in the E-V paradigm. The E-AV spelling paradigm also significantly improved the spelling accuracy and the raw bit rate compared with those in the E-V paradigm at one superposition (p < .05) and at two superpositions (p < .05). SIGNIFICANCE: The proposed emotion-based audiovisual spelling paradigm not only significantly improves the performance of the P300 speller, but also provides a basis for the development of various bimodal P300 speller systems, which is a step forward in the clinical application of brain-computer interfaces.

Single-molecule detection of biomarker and localized cellular photothermal therapy using an optical microfiber with nanointerface.

For early-stage diagnostics, there is a strong demand for sensors that can rapidly detect biomarkers at ultralow concentration or even at the single-molecule level. Compared with other types of sensors, optical microfibers are more convenient for use as point-of-care devices in early-stage diagnostics. However, the relatively low sensitivity strongly hinders their use. To this end, an optical microfiber is functionalized with a plasmonic nanointerface consisting of black phosphorus-supported Au nanohybrids. The microfiber is able to detect epidermal growth factor receptor (ErbB2) at concentrations ranging from 10 zM to 100 nM, with a detection limit of 6.72 zM, enabling detection at the single-molecule level. The nanointerface-sensitized microfiber is capable of differentiating cancer cells from normal cells and treating cancer cells through cellular photothermal therapy. This work opens up a possible approach for the integration of cellular diagnosis and treatment.

Real-time, in-situ analysis of silver ions using nucleic acid probes modified silica microfiber interferometry.

A sensitive Ag+ sensor based on nucleic acid probes modified silica microfiber interferometry is designed and developed. The probes on microfiber surface plays the part on catching Ag+ as tentacles, while their conformation change from random coils to hairpins. It induces the fiber surface refractive index change, which is captured by the optical fiber and translated into a significant wavelength shift in the interferometric fringe. Such a combination enables an improved concentration sensitivity of 0.22nm/log M and limit of detection of 1.36 × 10-9M, taking the advantage of real-time and in-situ analysis. It shows good selectivity in the present of many other metal ions and offers potential to analysis in real matrix, especially in the environmental samples must be analyzed in a short time. This may provide insights into the preparation of sensing platforms for optical quantification of other small molecular, supplementing the existing tools.

Effect of real-time cortical feedback in motor imagery-based mental practice training.

BACKGROUND: Mental practice using motor imagery of limb movement may facilitate motor recovery in persons who have experienced cerebrovascular accident (CVA). However, the lack of a feedback mechanism that can monitor the quality of the motor imagery affects patients' engagement and motivation to participate in the mental practice training program. OBJECTIVE: This study investigates the effect of novel real-time motor imagery-associated cortical activity feedback on motor imagery-based mental practice training. METHODS: Ten healthy volunteers were randomly assigned into intervention and control groups. Both groups participated in a five-visit motor imagery-based mental practice training program managed over a period of two months. The intervention group received mental practice training with real-time feedback of movement-associated cortical activity-beta band (16-28 Hz) event-related desynchronization (ERD) in electroencephalography (EEG), using a novel custom-made brain-computer interface (BCI) system. The control group received the mental practice training program without EEG cortical feedback. Motor excitability was assessed by measuring the frequency power magnitude of the EEG rhythmic activity associated with physical execution of wrist extension before and after the motor imagery-based mental practice training. RESULTS: The EEG frequency power magnitude associated with the physical execution of wrist extension was significantly lower (i.e. more desynchronized) after the mental practice training in the intervention group that received real-time cortical feedback (P < 0.05), whereas no significant difference in EEG frequency power magnitude associated with the physical execution of wrist extension was observed before and after mental practice training in the control group who did not receive feedback. CONCLUSIONS: The mental practice training program with motor imagery-associated cortical feedback facilitated motor excitability during the production of voluntary motor control. Motor imagery-based mental practice training with movement-associated cortical activity feedback may provide an effective strategy to facilitate motor recovery in brain injury patients, particularly during the early rehabilitation stage when full participation in physical and occupational therapy programs may not be possible due to excessive motor weakness.

Electroencephalography (EEG)-based brain-computer interface (BCI): a 2-D virtual wheelchair control based on event-related desynchronization/synchronization and state control.

This study aims to propose an effective and practical paradigm for a brain-computer interface (BCI)-based 2-D virtual wheelchair control. The paradigm was based on the multi-class discrimination of spatiotemporally distinguishable phenomenon of event-related desynchronization/synchronization (ERD/ERS) in electroencephalogram signals associated with motor execution/imagery of right/left hand movement. Comparing with traditional method using ERD only, where bilateral ERDs appear during left/right hand mental tasks, the 2-D control exhibited high accuracy within a short time, as incorporating ERS into the paradigm hypothetically enhanced the spatiotemoral feature contrast of ERS versus ERD. We also expected users to experience ease of control by including a noncontrol state. In this study, the control command was sent discretely whereas the virtual wheelchair was moving continuously. We tested five healthy subjects in a single visit with two sessions, i.e., motor execution and motor imagery. Each session included a 20 min calibration and two sets of games that were less than 30 min. Average target hit rate was as high as 98.4% with motor imagery. Every subject achieved 100% hit rate in the second set of wheelchair control games. The average time to hit a target 10 m away was about 59 s, with 39 s for the best set. The superior control performance in subjects without intensive BCI training suggested a practical wheelchair control paradigm for BCI users.

A motor imagery-based online interactive brain-controlled switch: paradigm development and preliminary test.

OBJECTIVE: To develop a practical motor imagery-based brain-controlled switch as functional as a real-world switch that is reliable with a minimal false positive operation rate and convenient for users without the need of attention to the switch during a 'No Control' state (when not to activate the switch). METHODS: Four healthy volunteers were instructed to perform an intended motor imagery task following an external sync signal in order to turn on a virtual switch provided on a computer screen. No specific mental task was required during the 'No Control' state. The beta band event-related frequency power (event-related desynchronization or ERD) from a single EEG Laplacian channel was monitored online in real-time. The computer continuously monitored the relative ERD power level until it exceeded a pre-set threshold and turned on the virtual switch. RESULTS: Subject 1 achieved lowest average false positive rate of 0.4+/-0.9% in a five-session online study during the entire 'No Control' state, whereby the subject required 6.8+/-0.6 s of active urging time or total response time of 20.5+/-1.9 s to perform repeated attempts in order to turn on the switch in the online interactive switch operation. The average false positive rate among four subjects was 0.8+/-0.4% with average active urging time of 12.3+/-4.4 s or average response time of 36.9+/-13.0 s. Offline analysis from subject 2 shows that the overall performance from 10-fold cross-validation was 96.2% with 3 consecutive epoch averaging, which was further improved to 99.0% by computationally intensive methods. CONCLUSIONS: The novel design of the brain-controlled switch using the ERD feature associated with motor imagery achieved minimal false positive rate with a reasonable active urging time or response time to activate the switch. SIGNIFICANCE: The reliability and convenience of the developed brain-controlled switch may extend current brain-computer interface capacities in practical communication and control applications.

Towards a user-friendly brain-computer interface: initial tests in ALS and PLS patients.

OBJECTIVE: Patients usually require long-term training for effective EEG-based brain-computer interface (BCI) control due to fatigue caused by the demands for focused attention during prolonged BCI operation. We intended to develop a user-friendly BCI requiring minimal training and less mental load. METHODS: Testing of BCI performance was investigated in three patients with amyotrophic lateral sclerosis (ALS) and three patients with primary lateral sclerosis (PLS), who had no previous BCI experience. All patients performed binary control of cursor movement. One ALS patient and one PLS patient performed four-directional cursor control in a two-dimensional domain under a BCI paradigm associated with human natural motor behavior using motor execution and motor imagery. Subjects practiced for 5-10min and then participated in a multi-session study of either binary control or four-directional control including online BCI game over 1.5-2h in a single visit. RESULTS: Event-related desynchronization and event-related synchronization in the beta band were observed in all patients during the production of voluntary movement either by motor execution or motor imagery. The online binary control of cursor movement was achieved with an average accuracy about 82.1+/-8.2% with motor execution and about 80% with motor imagery, whereas offline accuracy was achieved with 91.4+/-3.4% with motor execution and 83.3+/-8.9% with motor imagery after optimization. In addition, four-directional cursor control was achieved with an accuracy of 50-60% with motor execution and motor imagery. CONCLUSION: Patients with ALS or PLS may achieve BCI control without extended training, and fatigue might be reduced during operation of a BCI associated with human natural motor behavior. SIGNIFICANCE: The development of a user-friendly BCI will promote practical BCI applications in paralyzed patients.

Multisensory interactions elicited by audiovisual stimuli presented peripherally in a visual attention task: a behavioral and event-related potential study in humans.

We applied behavioral and event-related potential measurements to study human multisensory interactions induced by audiovisual (AV) stimuli presented peripherally in a visual attention task in which an irrelevant auditory stimulus occasionally accompanied the visual stimulus. A stream of visual, auditory, and AV stimuli was randomly presented to the left or right side of the subjects; subjects covertly attended to the visual stimuli on either the left or right side and promptly responded to visual targets on that side. Behavioral results showed that responses to AV stimuli were faster and more accurate than those to visual stimuli only. Three event-related potential components related to AV interactions were identified: (1) over the right temporal area, approximately 200 to 220 milliseconds; (2) over the centromedial area, approximately 290 to 310 milliseconds; and (3) over the left and right ventral temporal area, approximately 290 to 310 milliseconds. We found that these interaction effects occurred slightly later than those reported in previously published AV interaction studies in which AV stimuli were presented centrally. Our results suggest that the retinotopic location of stimuli affects AV interactions occurring at later stages of cognitive processing in response to a visual attention task.

Decoding human motor activity from EEG single trials for a discrete two-dimensional cursor control.

This study aims to explore whether human intentions to move or cease to move right and left hands can be decoded from spatiotemporal features in non-invasive EEG in order to control a discrete two-dimensional cursor movement for a potential multidimensional brain-computer interface (BCI). Five naïve subjects performed either sustaining or stopping a motor task with time locking to a predefined time window by using motor execution with physical movement or motor imagery. Spatial filtering, temporal filtering, feature selection and classification methods were explored. The performance of the proposed BCI was evaluated by both offline classification and online two-dimensional cursor control. Event-related desynchronization (ERD) and post-movement event-related synchronization (ERS) were observed on the contralateral hemisphere to the hand moved for both motor execution and motor imagery. Feature analysis showed that EEG beta band activity in the contralateral hemisphere over the motor cortex provided the best detection of either sustained or ceased movement of the right or left hand. The offline classification of four motor tasks (sustain or cease to move right or left hand) provided 10-fold cross-validation accuracy as high as 88% for motor execution and 73% for motor imagery. The subjects participating in experiments with physical movement were able to complete the online game with motor execution at an average accuracy of 85.5 +/- 4.65%; the subjects participating in motor imagery study also completed the game successfully. The proposed BCI provides a new practical multidimensional method by noninvasive EEG signal associated with human natural behavior, which does not need long-term training.

A high performance sensorimotor beta rhythm-based brain-computer interface associated with human natural motor behavior.

UNLABELLED: To explore the reliability of a high performance brain-computer interface (BCI) using non-invasive EEG signals associated with human natural motor behavior does not require extensive training. We propose a new BCI method, where users perform either sustaining or stopping a motor task with time locking to a predefined time window. Nine healthy volunteers, one stroke survivor with right-sided hemiparesis and one patient with amyotrophic lateral sclerosis (ALS) participated in this study. Subjects did not receive BCI training before participating in this study. We investigated tasks of both physical movement and motor imagery. The surface Laplacian derivation was used for enhancing EEG spatial resolution. A model-free threshold setting method was used for the classification of motor intentions. The performance of the proposed BCI was validated by an online sequential binary-cursor-control game for two-dimensional cursor movement. Event-related desynchronization and synchronization were observed when subjects sustained or stopped either motor execution or motor imagery. Feature analysis showed that EEG beta band activity over sensorimotor area provided the largest discrimination. With simple model-free classification of beta band EEG activity from a single electrode (with surface Laplacian derivation), the online classifications of the EEG activity with motor execution/motor imagery were: >90%/ approximately 80% for six healthy volunteers, >80%/ approximately 80% for the stroke patient and approximately 90%/ approximately 80% for the ALS patient. The EEG activities of the other three healthy volunteers were not classifiable. The sensorimotor beta rhythm of EEG associated with human natural motor behavior can be used for a reliable and high performance BCI for both healthy subjects and patients with neurological disorders. SIGNIFICANCE: The proposed new non-invasive BCI method highlights a practical BCI for clinical applications, where the user does not require extensive training.