An Ultrasensitive Ti3C2Tx MXene-based Soft Contact Lens for Continuous and Nondestructive Intraocular Pressure Monitoring.

Wearable soft contact lens sensors for continuous and nondestructive intraocular pressure (IOP) monitoring are highly desired as glaucoma and postoperative myopia patients grow, especially as the eyestrain crowd increases. Herein, a smart closed-loop system is presented that combines a Ti3C2Tx MXene-based soft contact lens (MX-CLS) sensor, wireless data transmission units, display, and warning components to realize continuous and nondestructive IOP monitoring/real-time display. The fabricated MX-CLS device exhibits an extremely high sensitivity of 7.483 mV mmHg-1, good linearity on silicone eyeballs, excellent stability under long-term pressure-release measurement, sufficient transparency with 67.8% transmittance under visible illumination, and superior biocompatibility with no discomfort when putting the MX-CLS sensor onto the Rabbit eyes. After integrating with the wireless module, users can realize real-time monitoring and warning of IOP via smartphones, the demonstrated MX-CLS device together with the IOP monitoring/display system opens up promising platforms for Ti3C2Tx materials as the base for multifunctional contact lens-based sensors and continuous and nondestructive IOP measurement system.

High-Density Electroencephalogram Facilitates the Detection of Small Stimuli in Code-Modulated Visual Evoked Potential Brain-Computer Interfaces.

In recent years, there has been a considerable amount of research on visual evoked potential (VEP)-based brain-computer interfaces (BCIs). However, it remains a big challenge to detect VEPs elicited by small visual stimuli. To address this challenge, this study employed a 256-electrode high-density electroencephalogram (EEG) cap with 66 electrodes in the parietal and occipital lobes to record EEG signals. An online BCI system based on code-modulated VEP (C-VEP) was designed and implemented with thirty targets modulated by a time-shifted binary pseudo-random sequence. A task-discriminant component analysis (TDCA) algorithm was employed for feature extraction and classification. The offline and online experiments were designed to assess EEG responses and classification performance for comparison across four different stimulus sizes at visual angles of 0.5°, 1°, 2°, and 3°. By optimizing the data length for each subject in the online experiment, information transfer rates (ITRs) of 126.48 ± 14.14 bits/min, 221.73 ± 15.69 bits/min, 258.39 ± 9.28 bits/min, and 266.40 ± 6.52 bits/min were achieved for 0.5°, 1°, 2°, and 3°, respectively. This study further compared the EEG features and classification performance of the 66-electrode layout from the 256-electrode EEG cap, the 32-electrode layout from the 128-electrode EEG cap, and the 21-electrode layout from the 64-electrode EEG cap, elucidating the pivotal importance of a higher electrode density in enhancing the performance of C-VEP BCI systems using small stimuli.

A Self-Rectifying Synaptic Memristor Array with Ultrahigh Weight Potentiation Linearity for a Self-Organizing-Map Neural Network.

Two-terminal self-rectifying (SR)-synaptic memristors are preeminent candidates for high-density and efficient neuromorphic computing, especially for future three-dimensional integrated systems, which can self-suppress the sneak path current in crossbar arrays. However, SR-synaptic memristors face the critical challenges of nonlinear weight potentiation and steep depression, hindering their application in conventional artificial neural networks (ANNs). Here, a SR-synaptic memristor (Pt/NiOx/WO3-x:Ti/W) and cross-point array with sneak path current suppression features and ultrahigh-weight potentiation linearity up to 0.9997 are introduced. The image contrast enhancement and background filtering are demonstrated on the basis of the device array. Moreover, an unsupervised self-organizing map (SOM) neural network is first developed for orientation recognition with high recognition accuracy (0.98) and training efficiency and high resilience toward both noises and steep synaptic depression. These results solve the challenges of SR memristors in the conventional ANN, extending the possibilities of large-scale oxide SR-synaptic arrays for high-density, efficient, and accurate neuromorphic computing.

Flexible terahertz metamaterial biosensor for label-free sensing of serum tumor marker modified on a non-metal area.

Terahertz (THz) metamaterials for rapid label-free sensing show application potential for the detection of cancer biomarkers. A novel flexible THz metamaterial biosensor based on a low refraction index parylene-C substrate is proposed. The biomarkers are modified on non-metal areas by a three-step modification method that simplifies the modification steps and improves the modified effectivity. Simulation results for non-metal modification illustrate that a bulk refractive index sensitivity of 325 GHz/RIU is achieved, which is larger than that obtained for the traditional metal modification (147 GHz/RIU). Meanwhile, several fluorescence experiments proved the uniform modification effect and selective adsorption capacity of the non-metal modification method. The concentration of the carcinoembryonic antigen (CEA) biomarkers for breast cancer patients tested using this THz biosensor is found to be consistent with results obtained from traditional clinical tests. The limit of detection reaches 2.97 ng/mL. These findings demonstrate that the flexible THz metamaterial biosensor can be extensively used for the rapid detection of cancer biomarkers in the future.

First Report of Root Rot Caused by Dactylonectria torresensis on Bletilla striata (Baiji) in Yunnan, China.

Bletilla striata (Thunb.) Rchb.f. (Orchidaceae family, known as Baiji in Chinese) is an endangered plant species with important medicinal value in China. Bletilla striata plants with symptoms of wilting, leaf yellowing and rotting on underground parts were found in Shizong (24.82822 N; 103.99084 E), Yunnan Province, China in July 2016. In the following years, this disease occurred and became prevalent when high temperature and high humidity prevailed in the fields from May to August. The incidence of the disease varied from 45 to 75%, with yield losses of 40 to 65% in different B. striata fields. To identify the causal agent of the disease, symptomatic vascular tissue fragments were soaked in 2% sodium hypochlorite for 2 min, rinsed twice with sterile distilled water, and then placed on 4% (w/v) potato dextrose agar (PDA) plates. The plates were incubated at 26°C in 12h light/dark for three days. Mycelia grown from the edges of the plant fragments were transferred to PDA plates and incubated at 26°C in 12h light/dark. After three days, hyphal tips were isolated from the edge of the colonies to PDA plates. Three hyphal-tip isolates from different plants were further studied. The colonies of these three isolates were dark red, with cottony mycelia of moderate density. Hyphae were transparent and branched. Numerous hyphae anastomosed frequently and formed hyphal coils. For further morphological analysis, sporulation was induced as described by Cabral et al. (2012) and Lombard et al. (2014). Macroconidia were abundant, 37.2 to 44.0 µm × 5.2 to 8.7 µm based on the measurement of 20 conidia from each isolate. Ascospores divided into two cells of equal size, ellipsoid to oblong-ellipsoid, 12.5 to 14.8 µm × 4.8 to 5.9 µm based on the measurement of 20 spores from each isolate. Conidiophores simple or complex, sporodochial. Simple conidiophores arising laterally or terminally from aerial mycelium, solitary to loosely aggregated, unbranched or sparsely brached, more or less cylindrical. These morphological characteristics were consistent with the description of Dactylonectria spp. by Cabral et al. (2012) and Lombard et al. (2014). From one isolate, the internal transcribed spacer (ITS) region of ribosomal DNA and the beta-tubulin (tub2) gene were amplified by polymerase chain reaction (PCR) using the primer pairs ITS1/ITS4 (White et al. 1990) and T1/Bt-2b (Cabral et al. 2012), respectively. PCR products were sequenced and deposited in GenBank with accession numbers MH458779 (ITS) and MH626485 (tub2). BLAST search revealed that both sequences showed 99 to 100% homology with the corresponding sequences of previously identified D. torresensis isolates. Specially, MH458779 shares 100% identity with the entire 463-base pair (bp) sequence of KP411806, the ITS sequence of a D. torresensis isolate identified from olive trees (Nigro et al. 2019); MH626485 shares 99% identity with the entire 320-bp sequence of KP411801, the tub2 sequence of the same olive tree isolate. In addition, the entire 609-bp sequence of MH626485 shares 99% identity with JF735478, the tub2 sequence of a D. torresensis isolate identified from grapevines (Cabral et al. 2012). To test the pathogenicity of the fungus, plants of B. striata in plastic pots filled with sterilized nursery soil were inoculated with each of the three isolates by placing a fungal-colonized wheat kernel adjacent to each health plant. Plants inoculated with noncolonized wheat kernels were used as controls. Plants in three pots (replicates), with one plant per pot, were inoculated by each isolate. The pots were maintained in a greenhouse with a 12h photoperiod at 25°C. Ten days after inoculation, black necrotic lesions identical to those observed in the field were evident on the roots of all inoculated plants. Using the same methods described above, fungi with identical morphologies as described above were isolated from lesions caused by each of the three isolates. The control plants remained healthy, and no fungus was re-isolated. This completed Koch's postulates. Based on the morphological characteristics and molecular identification, the pathogen was determined to be D. torresensis. To our knowledge, this is the first report of D. torresensis causing root rot of B. striata in Yunnan, China. It is important to further study the impacts of this new disease on B. striata production in China.

Exploring surface sensitivity of Rayleigh anomaly in metal/dielectric multilayer gratings.

Biosensors based on Rayleigh anomaly (RA) in metal gratings exhibit impressive bulk refractive index (RI) sensitivity and narrow linewidth. However, the electric field enhancement extends far away from surface of the gratings, which limits the application on biosensor where the RI changes are restricted at the sensor interface. To overcome this shortcoming, a novel grating composed of a 8-layer Au/Al2O3 stack was optimized by numerical simulation. The electric field is limited in several hundreds of nanometers from surface. The surface sensitivity increases 10 times than that of Au gratings at the detection depth of less than 400 nm. The surface index sensitivity can be improved 5 times under oblique incidence than that under normal incidence when the thickness of cover media is 20 nm.

Physical mechanism for the synapse behaviour of WTiOx-based memristors.

Tungsten-based memristors possess many advantages as candidates for memristive devices, including gradual changes in resistance states and memorization and learning functions. However, most previous reports mainly focus on studying synaptic learning rules instead of analysing the internal mechanism that results in the exterior learning rules. Herein, we discuss stacked Au/WTiOx/Au and Ti/WTiOx/Au devices in which the function of the resistance switch is realized by the externally induced local migration of oxygen ions. The consecutively adjustable multilevel resistance of the Au/WTiOx/Au device may be due to the variation in the barrier width and height in high oxygen vacancy concentrations. Additionally, the high and low resistance states of Ti/WTiOx/Au devices are considered as a result of the connection and rupture of the conductive filaments at low concentrations of oxygen vacancies. The physical mechanism construction and state-full synapse development through the control of ion migration provide insight into the applications of oxide-based memristors in neuromorphic computation.

An open dataset for human SSVEPs in the frequency range of 1-60 Hz.

A steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) system relies on the photic driving response to effectively elicit characteristic electroencephalogram (EEG) signals. However, traditional visual stimuli mainly adopt high-contrast black-and-white flickering stimulations, which are easy to cause visual fatigue. This paper presents an SSVEP dataset acquired at a wide frequency range from 1 to 60 Hz with an interval of 1 Hz using flickering stimuli under two different modulation depths. This dataset contains 64-channel EEG data from 30 healthy subjects when they fixated on a single flickering stimulus. The stimulus was rendered on an LCD display with a refresh rate of 240 Hz. Initially, the dataset was rigorously validated through comprehensive data analysis to investigate SSVEP responses and user experiences. Subsequently, BCI performance was evaluated through offline simulations of frequency-coded and phase-coded BCI paradigms. This dataset provides comprehensive and high-quality data for studying and developing SSVEP-based BCI systems.

Optimizing Visual Stimulation Paradigms for User-Friendly SSVEP-Based BCIs.

In steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) systems, traditional flickering stimulation patterns face challenges in achieving a trade-off in both BCI performance and visual comfort across various frequency bands. To investigate the optimal stimulation paradigms with high performance and high comfort for each frequency band, this study systematically compared the characteristics of SSVEP and user experience of different stimulation paradigms with a wide stimulation frequency range of 1-60 Hz. The findings suggest that, for a better balance between system performance and user experience, ON and OFF grid stimuli with a Weber contrast of 50% can be utilized as alternatives to traditional flickering stimulation paradigms in the frequency band of 1-25 Hz. In the 25-35 Hz range, uniform flicker stimuli with the same 50% contrast are more suitable. In the higher frequency band, traditional uniform flicker stimuli with a high 300% contrast are preferred. These results are significant for developing high performance and user-friendly SSVEP-based BCI systems.

A calibration-free c-VEP based BCI employing narrow-band random sequences.

Objective.Code-modulated visual evoked potential (c-VEP) based brain-computer interfaces (BCIs) exhibit high encoding efficiency. Nevertheless, the majority of c-VEP based BCIs necessitate an initial training or calibration session, particularly when the number of targets expands, which impedes the practicality. To address this predicament, this study introduces a calibration-free c-VEP based BCI employing narrow-band random sequences.Approach.For the encoding method, a series of random sequences were generated within a specific frequency band. The c-VEP signals were subsequently elicited through the application of on-type grid flashes that were modulated by these sequences. For the calibration-free decoding algorithm, filter-bank canonical correlation analysis (FBCCA) was utilized with the reference templates generated from the original sequences. Thirty-five subjects participated into an online BCI experiment. The performances of c-VEP based BCIs utilizing narrow-band random sequences with frequency bands of 15-25 Hz (NBRS-15) and 8-16 Hz (NBRS-8) were compared with that of a steady-state visual evoked potential (SSVEP) based BCI within a frequency range of 8-15.8 Hz.Main results.The offline analysis results demonstrated a substantial correlation between the c-VEPs and the original narrow-band random sequences. After parameter optimization, the calibration-free system employing the NBRS-15 frequency band achieved an average information transfer rate (ITR) of 78.56 ± 37.03 bits/min, which exhibited no significant difference compared to the performance of the SSVEP based system when utilizing FBCCA. The proposed system achieved an average ITR of 102.1 ± 57.59 bits/min in a simulation of a 1000-target BCI system.Significance.This study introduces a novel calibration-free c-VEP based BCI system employing narrow-band random sequences and shows great potential of the proposed system in achieving a large number of targets and high ITR.

A high-performance SSVEP-based BCI using imperceptible flickers.

Objective.Existing steady-state visual evoked potential (SSVEP)-based brain-computer interfaces (BCIs) struggle to balance user experience and system performance. This study proposed an individualized space and phase modulation method to code imperceptible flickers at 60 Hz towards a user-friendly SSVEP-based BCI with high performance.Approach.The individualized customization of visual stimulation took the subject-to-subject variability in cortex geometry into account. An annulus global-stimulation was divided into local-stimulations of eight annular sectors and presented to subjects separately. The local-stimulation SSVEPs were superimposed to simulate global-stimulation SSVEPs with 47space and phase coding combinations. A four-class phase-coded BCI diagram was used to evaluate the simulated classification performance. The performance ranking of all simulated global-stimulation SSVEPs were obtained and three performance levels (optimal, medium, worst) of individualized modulation groups were searched for each subject. The standard-modulation group conforming to the V1 'cruciform' geometry and the non-modulation group were involved as controls. A four-target phase-coded BCI system with SSVEPs at 60 Hz was implemented with the five modulation groups and questionnaires were used to evaluate user experience.Main results.The proposed individualized space and phase modulation method effectively modulated the SSVEP intensity without affecting the user experience. The online BCI system using the 60 Hz stimuli achieved mean information transfer rates of 52.8 ± 1.9 bits min-1, 16.8 ± 2.4 bits min-1, and 42.4 ± 3.0 bits min-1with individualized optimal-modulation, individualized worst-modulation, and non-modulation groups, respectively.Significance.Structural and functional characteristics of the human visual cortex were exploited to enhance the response intensity of SSVEPs at 60 Hz, resulting in a high-performance BCI system with good user experience. This study has important theoretical significance and application value for promoting the development of the visual BCI technology.

Implantable intracortical microelectrodes: reviewing the present with a focus on the future.

Implantable intracortical microelectrodes can record a neuron's rapidly changing action potentials (spikes). In vivo neural activity recording methods often have either high temporal or spatial resolution, but not both. There is an increasing need to record more neurons over a longer duration in vivo. However, there remain many challenges to overcome before achieving long-term, stable, high-quality recordings and realizing comprehensive, accurate brain activity analysis. Based on the vision of an idealized implantable microelectrode device, the performance requirements for microelectrodes are divided into four aspects, including recording quality, recording stability, recording throughput, and multifunctionality, which are presented in order of importance. The challenges and current possible solutions for implantable microelectrodes are given from the perspective of each aspect. The current developments in microelectrode technology are analyzed and summarized.

A new grid stimulus with subtle flicker perception for user-friendly SSVEP-based BCIs.

Objective.The traditional uniform flickering stimulation pattern shows strong steady-state visual evoked potential (SSVEP) responses and poor user experience with intense flicker perception. To achieve a balance between performance and comfort in SSVEP-based brain-computer interface (BCI) systems, this study proposed a new grid stimulation pattern with reduced stimulation area and low spatial contrast.Approach.A spatial contrast scanning experiment was conducted first to clarify the relationship between the SSVEP characteristics and the signs and values of spatial contrast. Four stimulation patterns were involved in the experiment: the ON and OFF grid stimulation patterns that separately activated the positive or negative contrast information processing pathways, the ON-OFF grid stimulation pattern that simultaneously activated both pathways, and the uniform flickering stimulation pattern that served as a control group. The contrast-intensity and contrast-user experience curves were obtained for each stimulation pattern. Accordingly, the optimized stimulation schemes with low spatial contrast (the ON-50% grid stimulus, the OFF-50% grid stimulus, and the Flicker-30% stimulus) were applied in a 12-target and a 40-target BCI speller and compared with the traditional uniform flickering stimulus (the Flicker-500% stimulus) in the evaluation of BCI performance and subjective experience.Main results.The OFF-50% grid stimulus showed comparable online performance (12-target, 2 s: 69.87 ± 0.74 vs. 69.76 ± 0.58 bits min-1, 40-target, 4 s: 57.02 ± 2.53 vs. 60.79 ± 1.08 bits min-1) and improved user experience (better comfortable level, weaker flicker perception and higher preference level) compared to the traditional Flicker-500% stimulus in both multi-targets BCI spellers.Significance.Selective activation of the negative contrast information processing pathway using the new OFF-50% grid stimulus evoked robust SSVEP responses. On this basis, high-performance and user-friendly SSVEP-based BCIs have been developed and implemented, which has important theoretical significance and application value in promoting the development of the visual BCI technology.

A wearable group-synchronized EEG system for multi-subject brain-computer interfaces.

Objective: The multi-subject brain-computer interface (mBCI) is becoming a key tool for the analysis of group behaviors. It is necessary to adopt a neural recording system for collaborative brain signal acquisition, which is usually in the form of a fixed wire. Approach: In this study, we designed a wireless group-synchronized neural recording system that supports real-time mBCI and event-related potential (ERP) analysis. This system uses a wireless synchronizer to broadcast events to multiple wearable EEG amplifiers. The simultaneously received broadcast signals are marked in data packets to achieve real-time event correlation analysis of multiple targets in a group. Main results: To evaluate the performance of the proposed real-time group-synchronized neural recording system, we conducted collaborative signal sampling on 10 wireless mBCI devices. The average signal correlation reached 99.8%, the amplitude of average noise was 0.87 µV, and the average common mode rejection ratio (CMRR) reached 109.02 dB. The minimum synchronization error is 237 µs. We also tested the system in real-time processing of the steady-state visual-evoked potential (SSVEP) ranging from 8 to 15.8 Hz. Under 40 target stimulators, with 2 s data length, the average information transfer rate (ITR) reached 150 ± 20 bits/min, and the highest reached 260 bits/min, which was comparable to the marketing leading EEG system (the average: 150 ± 15 bits/min; the highest: 280 bits/min). The accuracy of target recognition in 2 s was 98%, similar to that of the Synamps2 (99%), but a higher signal-to-noise ratio (SNR) of 5.08 dB was achieved. We designed a group EEG cognitive experiment; to verify, this system can be used in noisy settings. Significance: The evaluation results revealed that the proposed real-time group-synchronized neural recording system is a high-performance tool for real-time mBCI research. It is an enabler for a wide range of future applications in collaborative intelligence, cognitive neurology, and rehabilitation.

A high-frequency SSVEP-BCI system based on a 360 Hz refresh rate.

Objective. Steady-state visual evoked potential (SSVEP) based brain-computer interfaces (BCIs) often struggle to balance user experience and system performance. To address this challenge, this study employed stimuli in the 55-62.8 Hz frequency range to implement a 40-target BCI speller that offered both high-performance and user-friendliness.Approach. This study proposed a method that presents stable multi-target stimuli on a monitor with a 360 Hz refresh rate. Real-time generation of stimulus matrix and stimulus rendering was used to ensure stable presentation while reducing the computational load. The 40 targets were encoded using the joint frequency and phase modulation method, offline and online BCI experiments were conducted on 16 subjects using the task discriminant component analysis algorithm for feature extraction and classification.Main results. The online BCI system achieved an average accuracy of 88.87% ± 3.05% and an information transfer rate of 51.83 ± 2.77 bits min-1under the low flickering perception condition.Significance. These findings suggest the feasibility and significant practical value of the proposed high-frequency SSVEP BCI system in advancing the visual BCI technology.

Optimization of ear electrodes for SSVEP-based BCI.

Objective.Current ear electrodes often require complex placing or long stimulation durations to achieve good detection of steady-state visual evoked potential (SSVEP). To improve the practicability of ear electrode-based SSVEP-BCI (brain-computer interface) system, we developed a high-performance ear electrode that can be easily placed.Approach.Hydrogel based disposable and replaceable semi-dry electrodes are developed to improve the contact impedance and wear feeling. The best combination of electrodes for SSVEP-BCI application around the ear is optimized by assessing the electrode on volunteers, and the performance of the electrode was compared with that of the occipital electrode.Main results.The developed ear hydrogel electrode can achieve an impedance close to that of the wet electrode. Three combinations of ear electrode groups demonstrate high information transfer rate (ITR) and accuracy in SSVEP-BCI applications. According to the rating of the comprehensive assessment and BCI performance in the online session, the behind-aural electrode is the best electrode combination for recording SSVEP in the ear region. The average preparation time is the shortest, and the average impedance is the lowest. The ITR of the behind-aural electrode based SSVEP-BCI system can reach 37.5 ± 18 bits min-1. The stimulus duration was as low as 3 s compared to 5 s or 10 s in other studies.Significance.The accuracy, ITR, and wear feeling can be improved by introducing a semi-dry ear electrode and optimizing the position and the combination of ear electrode. By providing a better trade-off between performance and convenience, the ear electrode-based SSVEP-BCI promises to be used in daily life.

All-Optically Controlled Artificial Synapses Based on Light-Induced Adsorption and Desorption for Neuromorphic Vision.

Artificial synapses with the capability of optical sensing and synaptic functions are fundamental components to construct neuromorphic visual systems. However, most reported artificial optical synapses require a combination of optical and electrical stimuli to achieve bidirectional synaptic conductance modulation, leading to an increase in the processing time and system complexity. Here, an all-optically controlled artificial synapse based on the graphene/titanium dioxide (TiO2) quantum dot heterostructure is reported, whose conductance could be reversibly tuned by the effects of light-induced oxygen adsorption and desorption. Synaptic behaviors, such as excitatory and inhibitory, short-term and long-term plasticity, and learning-forgetting processes, are implemented using the device. An artificial neural network simulator based on the artificial synapse was used to train and recognize handwritten digits with a recognition rate of 92.2%. Furthermore, a 5 × 5 optical synaptic array that could simultaneously sense and memorize light stimuli was fabricated, mimicking the sensing and memory functionality of the retina. Such an all-optically controlled artificial synapse shows a promising prospect in the application of perception, learning, and memory tasks for future neuromorphic visual systems.

Flexible multichannel electrodes for acute recording in nonhuman primates.

Flexible electrodes have demonstrated better biocompatibility than rigid electrodes in relieving tissue encapsulation and long-term recording. Nonhuman primates are closer to humans in their brains' structural and functional properties, thus making them more suitable than rodents as animal models for potential clinical usage. However, the application of flexible electrodes on nonhuman primates has rarely been reported. In the present study, a flexible multichannel electrode array for nonhuman primates was developed and implemented for extracellular recording in behaving monkeys. To minimize the window of durotomy for reducing possible risks, a guide-tube-compatible implantation solution was designed to deliver the flexible electrodes through the dura into the cortex. The proposed structure for inserting flexible electrodes was characterized ex vivo and validated in vivo. Furthermore, acute recording of multichannel flexible electrodes for the primates was performed. The results showed that the flexible electrodes and implantation method used in this study meet the needs of extracellular recording in nonhuman primates. Task-related neuronal activities with a high signal-to-noise ratio of spikes demonstrated that our whole device is currently a minimally invasive and clinically viable approach for extracellular recording.

Hypothalamic warm-sensitive neurons require TRPC4 channel for detecting internal warmth and regulating body temperature in mice.

Precise monitoring of internal temperature is vital for thermal homeostasis in mammals. For decades, warm-sensitive neurons (WSNs) within the preoptic area (POA) were thought to sense internal warmth, using this information as feedback to regulate body temperature (Tcore). However, the cellular and molecular mechanisms by which WSNs measure temperature remain largely undefined. Via a pilot genetic screen, we found that silencing the TRPC4 channel in mice substantially attenuated hypothermia induced by light-mediated heating of the POA. Loss-of-function studies of TRPC4 confirmed its role in warm sensing in GABAergic WSNs, causing additional defects in basal temperature setting, warm defense, and fever responses. Furthermore, TRPC4 antagonists and agonists bidirectionally regulated Tcore. Thus, our data indicate that TRPC4 is essential for sensing internal warmth and that TRPC4-expressing GABAergic WSNs function as a novel cellular sensor for preventing Tcore from exceeding set-point temperatures. TRPC4 may represent a potential therapeutic target for managing Tcore.

An integrated device for patterning cells and selectively detaching.

Cell detachment is an ordinary cell behavior, and acts a significant role in numerous physiological processes. In addition, as massive cell groups have specific shapes in vivo, selectively controlling detachment of patterned cells is crucial for both clinical and fundamental research, because it may act as a platform for studying many processes in vitro, and also may be used for tissue engineering. However, it is difficult to first pattern cell groups into isolated islands and then to control their detachment dynamically. Herein, we developed an integrated device that could confine cell groups into various designed shapes, and selectively detach them by applying a low potential. This device contains electrode arrays (EAs) for cell pattern and detachment; and an automatic control system (ACS) connected to a computer for electrically controlling cell detachment. By microfabrication technology, EAs are fabricated on a glass substrate and isolated by surrounding insulating layer (Parylene-C). A new surface modification method is developed: within one step, oligopeptide (CCRRGDWLC) can bond to the gold surface of EAs for cell adhesion or detachment, and PLL-PEG grafts to other parts around the gold surface to resist cell adhesion simultaneously. When a low potential is applied by the ACS to the selected electrodes, cell groups on these electrodes would round up and detach from the surface. Comparing with previous methods, our method can first pattern cells and then selectively detach them. Besides, this device is easy to operate, fast response, and the detaching units are high through-put, and we believe it will be widely used in biological and medical labs.