In this work, we experimentally investigate the self-pulsating dynamics and excitability of two-section InP quantum-well lasers heterogeneously integrated on silicon. By appropriately tuning the electrical bias conditions, we realize multiple neuronal-like self-pulsating regimes, demonstrating resonate-and-fire and integrate-and-fire-like dynamics, highlighting the potential of the device as a high-speed photonic neuron. A systematic investigation of laser design parameters, including cavity length and gain/saturable absorber (SA) ratio, elucidates their impact on self-pulsation-related properties, such as pulse repetition frequency, and traces the operational parameter space that unlocks stable spiking. Finally, we demonstrate the basic attributes of integrate-and-fire dynamics in the integrated laser-neurons, paving the way toward scalable neuromorphic photonic integrated circuits (PIC) combining low-loss silicon synapses with versatile laser neurons.

The neuromuscular junction (NMJ) of larval Drosophila is widely used for studying synaptic transmission. Larval body wall muscles express five ionotropic glutamate receptor (iGluR) subunits that assemble into two tetrameric complexes, with subunit composition determining the strength and plasticity of synaptic transmission. Because NMJ function has been extensively characterized in larvae, it has commonly been assumed that adult fly NMJs share this molecular composition, despite substantial differences between life stages. Here, we systematically compare glutamate receptor expression across larval and adult Drosophila muscles. We find that adult leg and flight muscles exhibit different iGluR expression than larvae, lacking expression of several receptors previously considered essential. Adjacent muscles within the adult femur express distinct iGluRs, suggesting specialization of flexor and extensor muscles. Finally, the glutamate-gated chloride channel (GluClα) is expressed extrasynaptically in adult but not larval muscle fibers. Our results reveal unexpected heterogeneity in glutamate receptor expression across muscles and developmental stages, demonstrating the need for muscle-specific analyses in flies and other animals.

The activity of healthy neuronal networks is tightly regulated, and a shift toward hyperexcitability can cause various problems, such as epilepsies, memory deficits, and motor disorders. Numerous cellular, synaptic, and intrinsic mechanisms of hyperexcitability and compensatory mechanisms to restore healthy activity have been proposed. However, quantifying multiple compensatory mechanisms and their dependence on specific pathophysiological mechanisms has proven challenging, even in computational models. We use simulation-based inference to quantify the interactions of putative compensatory mechanisms in a spiking neuronal network model. Various parameters of the model can compensate for the changes in other parameters to maintain baseline activity, and we estimated their compensatory potential. Furthermore, specific causes of hyperexcitability - interneuron loss, excitatory recurrent synapses, and principal cell depolarization - have distinct compensatory mechanisms that can restore normal excitability. Our results show that spiking neuronal network simulators could generate hypotheses about the mechanisms of pathophysiological network mechanisms.

Operational instability remains a key obstacle for halide perovskites in neuromorphic optoelectronics, where sustained and reproducible photoresponses are required for in-sensor computing. Here, we report vapor-phase growth of composition-tunable two-dimensional (2D) inorganic perovskites, Cs x Rb1- x PbBr3 (0 ≤ x ≤ 1), and show that A-site cation alloying provides an effective route to simultaneously improve optical performance and structural robustness. By mapping the full Cs-Rb compositional space, we identify a narrow intermediate regime (x ≈ 0.8) where lattice strain is minimized and defect formation is suppressed. Perovskites in this regime exhibit substantially enhanced resistance to moisture, thermal stress and ion migration compared with either end member. These stability gains translate directly to device operation, enabling broadband photodetectors with fast response, high reproducibility and long-term durability. Using the optimized Cs0.81Rb0.19PbBr3 composition, we further demonstrate optoelectronic synaptic devices that reproduce key synaptic functions, including paired-pulse facilitation and light-programmable synaptic weights. Integrated into a spiking neural network, the devices enable real-time fire detection with 85% accuracy while maintaining stable performance over 7 days. This work establishes composition-engineered 2D inorganic perovskites as a robust platform for neuromorphic vision and energy-efficient in-sensor computing.

Immaturity of neurons in the adult hippocampal dentate gyrus (DG) has been implicated in the pathophysiology of neuropsychiatric disorders. Pseudo-immaturity of DG neurons can be induced by neuronal hyperexcitation in adulthood. This "dematuration," a reversal of maturation, could lead to aberrant neuronal maturation, if activated during development. However, it has not been directly tested whether dematuration can be induced in developing neurons. In the present study, we examined the effect of electroconvulsive treatment (ECT) on DG neurons of mice at several different developmental stages. Electrophysiological recordings were made using hippocampal slices. We analyzed frequency facilitation, a form of short-term synaptic plasticity, at the DG output mossy fiber synapses as an index of functional maturity of DG neurons. ECT had no significant effects on mossy fiber synaptic transmission at early postnatal ages, but it significantly reduced frequency facilitation at the postnatal age of ≥4 weeks, suggesting the induction of dematuration. Neuronal maturation marker analysis confirmed this result. The development of responsiveness to ECT was accompanied by maturation of N-methyl-D-aspartate receptor functions at the excitatory synaptic input onto DG neurons. Our results demonstrate that neuronal dematuration by ECT becomes inducible in postnatal 4 weeks in the DG of mice. Neuronal hyperexcitation such as seizures or alterations in N-methyl-D-aspartate receptor signaling around this developmental stage might affect proper maturation of DG neurons, thereby possibly increasing a risk of neuropsychiatric disorders.

Cytotoxic CD8[+] T cells induce target-cell death by producing effector proteases called granzymes. Most granzymes, as exemplified by granzyme B, induce apoptosis by cleaving intracellular substrates after delivery to target cells via the immunological synapse. By contrast, it was recently shown that granzyme K (GZMK), which is selectively expressed by a unique population of CD8[+] T cells, activates the complement cascade instead of executing direct cytotoxicity. In this Perspective, we summarize recent data on complement activation by CD8[+] T cell-derived GZMK that points to a novel lymphocyte-mediated pathway of complement activation. We present evidence that GZMK-expressing CD8[+] T cells have distinct pro-inflammatory effects in tissues and discuss their involvement in an array of chronic and inflammatory diseases. Furthermore, we propose the concept of 'tissue histotoxicity' as a core feature of GZMK-expressing CD8[+] T cells. We suggest this as a defence strategy that enables the immune system to act on a tissue neighbourhood instead of targeting one cell at a time. Finally, we discuss the possibility of GZMK expression being a heritable trait in subsets of memory T cells.

Macrophages phagocytose IgG-opsonized target cells by forming phagocytic synapses upon binding of IgG to Fcγ receptors (FcγR) expressed on the macrophage surface. However, binding requires accessibility of both IgG and FcγR within densely packed glycocalyces that decorate the macrophage and target cell surfaces. Here, we use cell-like target particles to show that non-binding 'bystander' proteins not directly involved in phagocytic signaling can sterically interfere with FcγR engagement, ultimately inhibiting synapse formation and phagocytosis. Furthermore, we demonstrate that adding a tall binding protein to the target particle overcomes bystander-mediated inhibition and substantially recovers phagocytosis in a process we call kinetic enhancement. We confirm that tall binders are sufficient to drive short binder engagement in vitro and introduce theory and simulations to explain the nonmonotonic dependence of phagocytosis on tall binder surface density. These findings show that kinetic enhancement is a general and tunable feature of interface formation, providing a strategy for re-engineering transition states to promote short receptor engagement at cell-cell contacts.

Two-dimensional ferroelectric materials offer opportunities for ultrathin non-volatile electronics, but their development is limited by stringent structural requirements for intrinsic polarity. Here we show that high-entropy engineering can induce switchable polarization in centrosymmetric van der Waals materials. By introducing configurational disorder into layered metal phosphorus trisulfides, we synthesize (MnFeCoNi)1-xCdxPS3 single crystals exhibiting electric-field-induced polar states and ferroelectric-like switching at ±0.5 V, with a transition temperature up to 523 K. Combined calculations and characterizations reveal that polarization originates from electric-field-driven Cd[2+] migration enabled by lattice distortions and heterogeneous coordination environments. This migration-mediated mechanism differs from conventional ferroelectric models and enables non-volatile neuromorphic functions, including long-term potentiation and bidirectional weight modulation. This work establishes high-entropy engineering as a strategy for manipulating ion migration dynamics in two-dimensional layered materials, opening a pathway toward emergent ferroelectric-like states beyond the conventional requirement of non-centrosymmetric structures.

CXC chemokine receptor 2 (CXCR2), a key member of the chemokine receptor family, plays a central role in regulating immune and inflammatory responses. Inflammation has been established as a critical pathological factor in various auditory disorders, including noise-induced hearing loss, drug-induced ototoxicity, and age-related hearing loss; however, the expression patterns and biological functions of CXCR2 in key cells involved in auditory signal transduction remain unclear. Here, we demonstrated that CXCR2 is abundantly expressed in cochlear spiral ganglion neurons (SGNs), hair cells, and the stria vascularis. Genetic deletion of CXCR2 resulted in progressive hearing loss in mice. SGNs from CXCR2 knockout mice exhibited increased expression of the Kv1.2 potassium channel, impaired ribbon synapses, and altered myelin integrity. Electrophysiological analysis revealed enhanced Kv1 currents and significantly reduced excitability in CXCR2-deficient SGNs. Notably, CXCR2 knockdown in SGNs using an adeno-associated virus recapitulated the hearing loss phenotype. In conclusion, our findings revealed that CXCR2 is essential for hearing as it regulates SGN excitability.

Listeners with clinically normal audiograms can still experience difficulty hearing in noise, a problem often discussed in the context of "hidden hearing loss". Cochlear synaptopathy has been proposed as one potential mechanism underlying these deficits, but reliable physiological assays for detecting synaptopathy remain challenging. The present study examined the effects of noise exposure that produced temporary threshold shift (TTS) in chinchillas using cochlear histology, noninvasive physiological measures, and single-unit auditory-nerve recordings. Histology confirmed persistent loss of inner-hair-cell synapses following exposure. ABR thresholds recovered and DPOAE levels were preserved 2 weeks after exposure, and many auditory-nerve response properties, including tuning and rate-level response metrics, showed no significant post-exposure differences among surviving fibers. However, several suprathreshold and timing-related abnormalities persisted after exposure. Suprathreshold ABR measures showed reduced Peak 1 amplitudes and prolonged Peak 5-Peak 1 latencies, while single-unit recordings revealed a reduced proportion of low-SR fibers in the exposed population. Selective post-exposure differences were also observed in auditory-nerve timing and modulation-related metrics, including reduced first-spike timing variability, increased adapted firing rate, reduced envelope-coding strength, and prolonged envelope-coding delay, suggesting residual disruption of suprathreshold temporal coding that may be perceptually relevant for listening in noise. These findings suggest that recovered TTS produces subtle but persistent neural changes that are not fully captured by conventional threshold-based measures. The results may help explain why diagnosis of cochlear synaptopathy remains challenging, and support the use of suprathreshold, latency-sensitive, and modulation-based physiological assays to detect residual neural effects of cochlear synaptopathy.

Children's long-term outcomes correlate with the physical and social features of the homes, schools, and neighborhoods in which they grow up. Yet, current techniques for establishing these correlations are limited. This article (a) presents five main issues linked to the currently used approaches. For example, most research relies on questionnaires or coding brief videoed interactions, which focus on a limited set of dimensions selected by researchers ("top-down" approach). As a result, these methods are limited because they provide only a static snapshot, which often conflates conceptually diverse levels, including the physical (e.g., noise, light) and social environments (e.g., caregiver mood, responsiveness). New technologies offer alternative approaches to these issues. This article (b) highlights how continuous multifeature observations, processed using machine learning tools, can improve our description of early development and inform theorizing of the mechanisms through which environments shape outcomes. Devices worn by children and those around them provide long-form recordings, allowing researchers to track how naturalistic environments vary over time and how children respond to them in real time. This shift supports a more dynamic, bottom-up, data-driven, and potentially culturally neutral approach to characterizing environmental variability. Finally, the article (c) discusses key limitations, notably the need to ensure that machine learning methods used to analyze early environments are trained using culturally diverse data, evaluating remaining risks of bias, and practical and ethical considerations. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

The skin and nervous system engage in bidirectional communication. Disruption is implicated in inflammatory, neuropathic and metabolic disorders. To systematically review the structural and functional basis of skin-nerve interactions in health and disease, following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A systematic search of PubMed (inception to June 10, 2026) combined MeSH and free-text terms for skin innervation, sensory neurons, sympathetic nervous system, neuropeptides, neuroimmune regulation, and skin diseases. Manual supplementation via reference tracing and author searches improved recall. 86 original studies were ultimately included (45 from database search and 41 from manual supplementation). Key findings: (1) Keratinocytes, Merkel, Langerhans and melanocytes form synapse-like connections with nerve endings, establishing a "sensory epithelium." (2) Substance P activates mast cells via neurokinin 1 receptor/mas-related G protein-coupled receptor X2 (neurogenic inflammation); while calcitonin gene-related peptide inhibits dendritic cells (immune tolerance). (3) In atopic dermatitis, stress recruits basophils/eosinophils via sympathetic-beta-2 adrenergic receptor axis; in psoriasis, TRPV1+ neurons activate the interleukin-23/interleukin-17 axis via calcitonin gene-related peptide. (4) Stress induces sensory neurons to release miR-let-7b, exacerbating psoriasis via macrophage Toll-like receptor 7. (5) Postherpetic neuralgia: intraepidermal nerve fiber density < 650 neurites/mm2 correlates with central hyperexcitability ("phantom pain"). (6) Neurofibromatosis type 1 (RAS) and guanine nucleotide-binding protein G(q) subunit alpha (ANGPT2) mutations reveal mechanisms for tumors or vascular malformations. (7) Heat stress induces skin kallikrein-related peptidase 14 to reprogram hypothalamic LRRC7+ astrocytes via blood, forming a "heat memory" that leads to metabolic disorders (reversed by vitamin A). Substance P/neurokinin 1 receptor, sensory nerve-calcitonin gene-related peptide-interleukin-23, sympathetic-beta-2 adrenergic receptor-basophil/eosinophil, and skin-hypothalamic circuits are key translational pathways. Targeting these (neurokinin 1 receptor antagonists, β-blockers, anti-calcitonin gene-related peptide antibodies, and vitamin A) offers therapeutic opportunities for inflammatory skin diseases, neuropathic itch/pain and stress-related metabolic disorders.

Nonvolatile memories based on two-dimensional (2D) van der Waals (vdW) heterostructures have attracted considerable attention because of their atomic-scale thickness, low energy operation, and prolonged data storage capability. However, most reported vdW floating-gate memories employ a bottom-floating-gate configuration, which often leads to a limited on/off ratio due to charge leakage and substrate-induced disturbance. Herein, a top-floating-gate memory based on a graphene (Gr)/h-BN/SnS2 vdW heterostructure is demonstrated, in which the top graphene layer serves as the charge-trapping layer. The device exhibits excellent nonvolatile memory performance, including an on/off ratio of 106, a memory window of 50.8 V, a low standby current of 1 pA, and an extrapolated retention time of 10 years. Owing to the low hole-tunneling barrier between SnS2 and h-BN, the device achieves more than 50 progressively modulated conductance levels under a weak optical pulse of 0.74 nW·mm-2. Moreover, stable long-term potentiation and depression characteristics can be regulated by optical and electrical pulses. Based on these synaptic behaviors, a three-layer multilayer perceptron neural network using the floating-gate memory achieved a classification accuracy of 96% for handwritten digit recognition using the Modified National Institute of Standards and Technology (MNIST) dataset. This work presents a top-floating-gate architecture for 2D-material memories, providing a feasible strategy for future logic-in-memory and neuromorphic computing applications.

Quadriceps weakness is a major determinant of disability in knee osteoarthritis (KOA), particularly in later life, yet weakness often exceeds the loss of muscle size. This discrepancy is clinically important because joint-derived activation failure occurs against a background of declining neuromuscular and regenerative reserve. We critically examine an evidence-bounded joint-afferent-motor unit framework in which abnormal afferent input from the diseased knee reduces effective neural drive through arthrogenic muscle inhibition (AMI). Persistent under-recruitment may be associated with altered motor-unit behavior and loading, impaired muscle quality, and greater reliance on compensatory reinnervation. We deliberately distinguish demonstrated human observations from provisional transitions and hypothesis-generating mechanistic extensions. Human evidence supports AMI and impaired muscle quality and provides preliminary cross-sectional evidence of altered motor-unit behavior; however, human studies have not established a temporal sequence from persistent AMI to motor-unit remodeling or denervation-reinnervation. Direct KOA-related neuromuscular junction (NMJ) evidence remains predominantly preclinical, and progressive NMJ degeneration has not been demonstrated in humans with KOA. Aging, sex, obesity, diabetes, systemic inflammation, pain sensitization, inactivity, and other comorbidities are treated as effect modifiers and competing explanations rather than proof of causation. We propose a testable, multimodal validation strategy combining joint imaging, standardized voluntary-activation testing, neurophysiology, high-density electromyography, motor-unit-number estimation, muscle imaging, and, when justified, tissue-level NMJ phenotyping. For older adults, the practical implication is mechanism-directed care: restore joint-related activation when inhibition dominates, use neural augmentation to enable adequate loading, address muscle-quality and metabolic constraints when present, and reserve NMJ-directed interventions for future human subgroups defined by convergent structural and physiological evidence.