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Consensus and synchronous firing in neural activities are relative to the physical properties of synaptic connections. For coupled neural circuits, the physical properties of coupling channels control the synchronization stability, and transient period for keeping energy diversity. Linear variable coupling results from voltage coupling via linear resistor by consuming certain Joule heat, and electric synapse coupling between neurons derives from gap junction connection under special electrophysiological condition. In this work, a voltage-controlled electric component with quadratic relation in the i–v (current–voltage) is used to connect two neural circuits composed of two variables. The energy function obtained by using Helmholtz theorem is consistent with the Hamilton energy function converted from the field energy in the neural circuit. Chaotic signals are encoded to approach a mixed signal within certain frequency band, and then its amplitude is adjusted to excite the neuron for detecting possible occurrence of nonlinear resonance. External stimuli are changed to trigger different firing modes, and nonlinear coupling activates changeable coupling intensity. It is confirmed that nonlinear coupling behaves functional regulation as hybrid synapse, and the synchronization transition between neurons can be controlled for reaching possible energy balance. The nonlinear coupling is helpful to keep energy diversity and prevent synchronous bursting because positive and negative feedback is switched with time. As a result, complete synchronization is suppressed and phase lock is controlled between neurons with energy diversity. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy combined with immune checkpoint inhibitors (IC), bevacizumab (BC), or both (IBC) is the preferred first-line therapy for PD-L1-negative and oncogenic-driver wild-type metastatic lung adenocarcinoma. However, the optimal strategy is still undetermined. Methods: This retrospective study enrolled PD-L1-negative metastatic lung adenocarcinoma patients from four cancer centers between January 1, 2018 and June 30, 2022. All the patients received IC, BC, or IBC as the first-line therapies. The efficacy and safety were evaluated. Results: A total of 205 patients were included, with 60, 83, and 62 patients in IC, BC, and IBC groups, respectively. The baseline characteristics among three groups were well balanced. Patients treated with IBC had the highest objective response rate (ORR) (43.5%) and disease control rate (DCR) (100%) relative to those treated with IC (40.4%, 84.2%) or BC (40.5%, 96.2%) (ORR: P = 0.919, DCR: P < 0.01). Compared with the IC (6.74 m) or BC (8.28 m), IBC treatment significantly improved median progression-free survival (mPFS) (9.53 m, P = 0.005). However, no difference in overall survival (OS) was observed. When stratified by different clinical and molecular information, we found that male gender, ever smoking, wild-type genes mutations, and adrenal metastasis predict superior PFS benefit when treated with IBC. In patients with liver metastasis, IBC or BC treatment displayed better PFS compared with IC. No additional adverse reactions were observed in IBC group compared with other two groups. Conclusion: Combined IBC treatment achieved superior DCR and PFS compared with IC or BC in patients with PD-L1-negative metastatic lung adenocarcinoma, while did not increase the adverse events. [ABSTRACT FROM AUTHOR]

A variety of nonlinear circuits can be tamed to reproduce the main dynamical properties in neural activities for biological neurons while designing reliable artificial synapses for connecting these neural circuits becomes a challenge. In this paper, a Josephson junction is used to build coupling channel for connecting two FitzHugh-Nagumo neural circuits driven by periodical voltage source. The hybrid synapse is designed by using a linear resistor paralleled with a Josephson junction, which can estimate the effect of external magnetic field by generating additive phase error between the junction. Indeed, it activates nonlinear coupling due to phase diversity in the Josephson junction. The coupled circuits are estimated in dimensionless dynamical systems by applying scale transformation on the variables and parameters in neural circuits. In fact, the intrinsic parameters of coupling channel are adjusted to detect the occurrence of synchronization. Bifurcation analysis is calculated to predict and confirm the occurrence of synchronization between two neural circuits. It is found that synchronization can be stabilized between two FHN neural circuits by selecting appropriate values for parameters in the Josephson junction involved in the coupling channel. It gives useful guidance for implementing artificial synapse for signal processing in neural circuits. [ABSTRACT FROM AUTHOR]

Raman backscattering spectroscopy and X-ray photoelectron spectroscopy have been applied to study thermal evolution of point defects as a function of post-annealing temperature in nitrogen-implanted ZnO thin films (ZnO:N). Zni-related donor defects (e.g., Zni-NO complexes or Zni clusters) are prone to dissociation to form a freely moving isolated Zni defect by post-annealing process, which is extremely advantageous for achieving a p-type transition of the ZnO:N film. However, lots of Ni atoms induced by ion implantation could migrate to the near-surface of the films to form NC/NH/NO species with increasing post-annealing temperature, resulting in a lower concentration of NO acceptor defects in ZnO:N films. In addition, although post-annealing at higher temperatures can form more No acceptor defects, the newly generated (N2)O double donor defects have a severe self-compensating effect. Consequently, the concentration of both the Zni-related donors and effective acceptors gradually decreases at elevated post-annealing temperatures, which is the reason why all ZnO:N films present n-type conductivity and do not convert to p-type conductivity. [ABSTRACT FROM AUTHOR]

Played as an important nonlinear electric device, memristor is often used to build a variety of nonlinear circuits, which can produce a variety of modes in oscillation. Due to the memory effect, the dynamics of nonlinear circuits involved with memristor can show distinct transition in oscillation between periodic and chaotic states when the initial values are changed. As a result, a generic initial-dependent dynamical system is built and its memory on initial setting is explained. The physical properties and potential mechanism for resistor-based voltage coupling, memristor coupling, capacitor-based and inductor-based field coupling are explained, respectively. In this review, scale transformation, application of memristor on neurodynamics, time delay, synchronization pattern, particularly, electromagnetic induction and radiation, neuron model setting under field effect, field coupling on signal propagation between nonlinear circuits and neurons are summarized for readers' extensive investigation. [ABSTRACT FROM AUTHOR]

The signal propagation and information encoding in neurons are much dependent on the activation of synapses function. Electric synapse often plays short-range modulation so that neurons can give fast responses to external stimulus while chemical synapse keeps active under long-range modulation on neural activities. Each neuron can be considered as an intelligent signal processor and appropriate setting in parameters in the electric devices can build reliable neural circuits to detect effective signal exchange and propagation. In this paper, a two-variable FitzHugh–Nagumo electrical oscillator driven by a sinusoidal voltage source is used to investigate the synchronization when the coupling capacitor is activated, which both of the plates of the coupling capacitor can trigger time-varying electric field in the capacitor, and energy flow is propagated to modulate the outputs of neural circuits. The circuit equations are obtained, and scale transformation is applied to get a dimensionless dynamical system under field coupling, and the error function for output voltage and phases is calculated to judge whether complete synchronization and phase synchronization can be realized by selecting different capacitances for the coupling capacitor. It is found that synchronization realization between neurons can be controlled by adjusting the capacitance of coupling capacitor. For two identical neurons driven by the same stimulus, complete synchronization is reached, while phase synchronization is stabilized when neurons are driven by different stimuli as the capacitor coupling is switched on. Furthermore, the realization of complete synchronization is verified on the analog circuits. It provides another new scheme for synchronization realization between neurons and a new mechanism for signal encoding in neurons via field coupling is explained. [ABSTRACT FROM AUTHOR]

Nonlinear chaotic circuits can be mapped into dimensionless dynamical systems by applying scale transformation. For synchronization control, linear voltage coupling via resistor has confirmed its effectiveness by applying negative feedback on the coupled circuits and nonlinear systems. In fact, resistor-based voltage coupling just bridges the electric devices of nonlinear circuits by imposing appropriate feedback current. Indeed, inductor (or induction coil) can also connect the electric devices and input appropriate stimulus feedback as induced electromotive force, and thus the coupled circuits can be regulated. In this paper, two Chua circuits are coupled by an inductor, which connects one capacitor of the coupled Chua circuits, and magnetic field coupling is activated because time-varying magnetic field and induced electromotive force are generated in the coupling inductor. For numerical approach and dynamical analysis, scale transformation is applied to get dimensionless dynamical systems under magnetic field coupling. Then the controllable parameter mapped from the coupling inductor is adjusted carefully to detect the synchronization approach. The same investigation is also carried out on the circuit platform Multisim. It is found that inductor coupling can benefit the realization of synchronization between two chaotic Chua systems. Complete synchronization can be reached between two identical circuits when the inductor coupling is activated with appropriate intensity. While phase synchronization can be stabilized between two non-identical circuits, chaotic oscillation can be suppressed by periodic Chua circuit under inductor coupling. The potential mechanism for inductor-based synchronization can be explained as magnetic field coupling, which field energy can be propagated via the coupling inductor with time-varying induced electromotive force, and it can give possible insights to know the information encoding between neurons and neural circuits. [ABSTRACT FROM AUTHOR]

Neuron can receive electric signals or forcing currents from more than one channel, and these forcing currents could show some diversity. Based on the Hindmarsh-Rose neuron model, mixed forcing currents, which are composed of low-frequency, high-frequency and constant signals, are imposed on the neuron, and multiple modes of electric activities could be observed alternately (in turn) from the neuron. Based on the Helmholtz theorem, the Hamilton energy is calculated to discern the energy dependence on the mode selection of the electric activities of neuron. It is found that the response of electrical activities much depends on the amplitude than the frequency when mixed signals are imposed on the neuron synchronously; however, the rhythm of electrical activities could be adjusted by the frequency of the periodical signals in the mixed signal. It is confirmed that the energy is much dependent on the mode of electrical activities instead of the external forcing currents directly, and a smaller energy occurs under bursting states. The delayed response of Hamilton energy to external forcing currents confirms that neuron contributes to energy coding. These results could be helpful for further investigation on energy problems in neuronal network associated with model transition for collective behaviors. [ABSTRACT FROM AUTHOR]

The fluctuation of intracellular and extracellular ion concentration induces the variation of membrane potential, and also complex distribution of electromagnetic field is generated. Furthermore, the membrane potential can be modulated by time-varying electromagnetic field. Therefore, magnetic flux is proposed to model the effect of electromagnetic induction in case of complex electrical activities of cell, and memristor is used to connect the coupling between membrane potential and magnetic flux. Based on the improved neuron model with electromagnetic induction being considered, the bidirectional coupling-induced synchronization behaviors between two coupled neurons are investigated on Spice tool and also printed circuit board. It is found that electromagnetic induction is helpful for discharge of neurons under positive feedback coupling, while electromagnetic induction is necessary to enhance synchronization behaviors of coupled neurons under negative feedback coupling. The frequency analysis on isolate neuron confirms that the frequency spectrum is enlarged under electromagnetic induction, and self-induction effect is detected. These experimental results can be helpful for further dynamical analysis on synchronization of neuronal network subjected to electromagnetic radiation. [ABSTRACT FROM AUTHOR]

The electric activities of neurons are dependent on the complex electrophysiological condition in neuronal system, and it indicates that the complex distribution of electromagnetic field could be detected in the neuronal system. According to the Maxwell electromagnetic induction theorem, the dynamical behavior in electric activity in each neuron can be changed due to the effect of internal bioelectricity of nervous system (e.g., fluctuation of ion concentration inside and outside of cell). As a result, internal fluctuation of electromagnetic field is established and the effect of magnetic flux across the membrane should be considered during the emergence of collective electrical activities and signals propagation among a large set of neurons. In this paper, the variable for magnetic flow is proposed to improve the previous Hindmarsh-Rose neuron model; thus, a four-variable neuron model is designed to describe the effect of electromagnetic induction on neuronal activities. Within the new neuron model, the effect of magnetic flow on membrane potential is described by imposing additive memristive current on the membrane variable, and the memristive current is dependent on the variation of magnetic flow. The dynamics of this modified model is discussed, and multiple modes of electric activities can be observed by changing the initial state, which indicates memory effect of neuronal system. Furthermore, a practical circuit is designed for this improved neuron model, and this model could be suitable for further investigation of electromagnetic radiation on biological neuronal system. [ABSTRACT FROM AUTHOR]

Target wave and spiral wave can regulate the collective behaviors of electrical activities in neuronal systems as a powerful 'pacemaker'. Disordered states occur when normal signal propagation among neurons is disturbed and neuronal disease could be induced. In this paper, a stable rotating spiral wave is developed as initial state that the two-dimensional neuronal network of Hindmarsh-Rose neuron shows distinct periodicity and regularity in space, and then, some parameters are changed sharply to model the destruction effect induced by external large forcing or internal collapse, and the destructed areas will be expanded to occupy a larger area by expanding the damaged boundary in random way. The collapse and instability of spiral wave, ordered states could be predicated by monitoring and analyzing the time series of some nodes. It could be useful to detect the emergence of disaster in some biological or ecological systems. [ABSTRACT FROM AUTHOR]

Autapse connected to the neuron can change the electric activity of neuron. The effect of autapse on neuronal activity is often described by adding an additive forcing current along a close loop, which is described by a time-delayed feedback on the membrane potential. Neuron often responds to electric autapse forcing sensitively and quickly, while the chemical autapse changes the electric activity of neuron slowly. By applying external forcing, a shift transition of electric activity can be more easily induced by the electric autapse than the chemical autapse. Our results confirm that chemical autapse can enhance and/or suppress the transition of electric activity with excitable or inhibitory type driven by electric autapse, vice versa. It indicates that an appropriate switch-off-on for autapse can make the neuron give different types of response to external forcing. Particularly, cooperation and competition between chemical and electric autapse help neuron response to external forcing in the most reliable way. [ABSTRACT FROM AUTHOR]

ETS gene fusions involving ERG, ETV1, ETV4, ETV5, and FLI1 define a distinct class of prostate cancer (PCa), and this might have a bearing on diagnosis, prognosis, and rational therapeutic targeting. In the current study, we focused on the clinicopathological significance of ETV4 in Chinese PCa patients and the mechanisms whereby ETV4 overexpression mediates tumor invasion in the prostate. Overall, ETV4 overexpression was identified in 30.4 % (45/148) of PCa cases by immunohistochemistry. Accordingly, ETV4 was rearranged in only 1.6 % (2/128) of PCa patients. Clinically, ETV4 overexpression was significantly correlated with Gleason score ( P = 0.045) and pathological tumor stage ( P = 0.041). Multivariate Cox regression analysis indicated that ETV4 is an unfavorable independent prognostic factor ( P = 0.040). Functional studies further showed that small interfering RNA (siRNA) knockdown of ETV4 significantly decreases proliferation and invasion of PC-3 cell and partially reverses epithelial-mesenchymal transition in vitro. Notably, ETV4 knockdown significantly downregulated expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) at messenger RNA (mRNA) and protein levels. Chromatin immunoprecipitation assay demonstrated that ETV4 regulates uPA expression through direct binding to its promoter region. Additionally, ETV4 knockdown was also observed to significantly inhibit expression of matrix metalloproteinase (MMP)-2 and MMP-9. In conclusion, for the first time, our study suggested that ETV4 is an independent poor prognostic factor in Chinese PCa patients. Silencing of ETV4 suppresses invasion of PCa cells by inhibiting the expression of uPA/uPAR as well as MMPs. Further studies will be needed to determine whether ETV4 could be regarded as a potential target for the management and prevention of PCa. [ABSTRACT FROM AUTHOR]

Autapse is a type of synapse that connects axon and dendrites of the same neuron, and the effect is often detected by close-loop feedback in axonal action potentials to the owned dendritic tree. An artificial autapse was introduced into the Hindmarsh-Rose neuron model, and a regular network was designed to detect the regular pattern formation induced by autapse. It was found that target wave emerged in the network even when only a single autapse was considered. By increasing the (autapse density) number of neurons with autapse, for example, a regular area (2×2, 3×3, 4×4, 5×5 neurons) under autapse induced target wave by selecting the feedback gain and time-delay in autapse. Spiral waves were also observed under optimized feedback gain and time delay in autapses because of coherence-like resonance in the network induced by some electric autapses connected to some neurons. This confirmed that the electric autapse has a critical role in exciting and regulating the collective behaviors of neurons by generating stable regular waves (target waves, spiral waves) in the network. The wave length of the induced travelling wave (target wave, spiral wave), because of local effect of autapse, was also calculated to understand the waveprofile in the network of neurons. [ABSTRACT FROM AUTHOR]

The effect of autapse on adjusting the membrane of potentials of neuron is described by imposing a time-delayed feedback on the membrane of neuron in a close loop type, and the Hindmarsh-Rose (HR) neuron under autapse is investigated. Firstly, the electric activity of single HR neuron under electric autapse and chemical autapse is investigated. It is found that quiescent neuron is activated due to appropriate time delay and feedback gain in the autapse, and the autapse plays an important role in waking up neuron. The parameter region for periodic, chaotic activity of neuron under autapse is calculated in a numerical way, and transition from spiking to bursting is observed by increasing the feedback gain and time delay carefully. Furthermore, the collective electric activities of neurons in a ring network is investigated and abundant electric activities are observed due to the competition between the autapse and the time-delayed coupling between adjacent neurons in the network, and time delay in coupling between neurons also plays an important role in enhancing synchronization in the network. [ABSTRACT FROM AUTHOR]

Some experimental results have confirmed that a spiral wave could be observed in the cortex of brain. The biological Hodgkin-Huxley neurons are used to construct a regular network with nearest-neighbor connection, artificial line defects are generated to block the traveling wave in the network, and the potential mechanism for formation of spiral wave is investigated. A target wave is generated in a local area by imposing two external forcing currents with diversity ( I− I) in different areas of the network. It is confirmed that spiral wave could be induced by the defects even if no specific initial values are used. A single perfect spiral wave can occupy the network when the coupling intensity exceeds certain threshold; otherwise, a group of spiral waves emerges in the network. Certain channel noise can enhance the diversity ( I− I) for generating target wave, and then spiral waves are induced by blocking the target wave with defects under no-flux and/or periodic boundary conditions in the network. [ABSTRACT FROM AUTHOR]

The electric activities of neurons could be changed when ion channel block occurs in the neurons. External forcing currents with diversity are imposed on the regular network of Hodgkin-Huxley (HH) neuron, and target waves are induced to occupy the network. The forcing current I is imposed on neurons in a local region with m× m nodes in the network, neurons in other nodes are imposed with another forcing current I. Target wave could be developed to occupy the network when the gradient forcing current ( I- I) exceeds certain threshold, and the formation of target wave is independent of the selection of boundary condition. It is also found that the developed target wave can decrease the negative effect of ion channel block and suppress the spiral wave, and thus channel noise is also considered. The potential mechanism of formation of target wave could be that the gradient forcing current ( I- I) generates quasi-periodical signal in local area, and the propagation of quasi-periodical signal induces target-like wave due to mutual coupling among neurons in the network. [ABSTRACT FROM AUTHOR]