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Data-driven reduced modeling of neural dynamics

Abstract Neural ordinary differential equations (ODEs) are widely used in neuroscience to model the collective activity of neurons during behavioral tasks. The high dimensionality of their parameter and activity spaces, however, often make it challenging to infer and interpret the fundamental features of their dynamics. In this study, we employ recent nonlinear dynamical system techniques to uncover the core dynamics of several Neural ODEs used in contemporary neuroscience. Specifically, using a data-driven approach, we identify Spectral Submanifolds (SSMs), i.e., low-dimensional attracting invariant manifolds tangent to the eigenspaces of fixed points. The internal dynamics of SSMs serve as nonlinear models that reduce the dimensionality of the full RNNs by orders of magnitude. Through low-dimensional, SSM-reduced models, we give mathematically precise definitions of line and ring attractors, which are intuitive concepts commonly used to explain decision-making and working memory. This unprecedented level of understanding of Neural ODEs obtained from SSM reduction enables the interpretation of mathematically well-defined and robust structures in neuronal dynamics, leading to predictions about the neural computations underlying behavior.

Medial Prefrontal Cortex Innervation of the Basal Forebrain Regulates Behavioral Activation with Prelimbic and Infralimbic Projections Contributing to Distinct Affective Functions in Rats

The medial prefrontal cortex (mPFC) regulates affective and motivational behaviors through its projections to subcortical targets, yet the functional contribution of its innervation of the basal forebrain (BF) remains poorly understood. Here, we combined viral tracing, neural activity mapping, molecular characterization, and pathway-specific optogenetic manipulations in adult rats (27 males, 28 females) to investigate the role of prelimbic (PrL) and infralimbic (IL) projections to BF. Using retrograde tracing combined with stress-induced c-Fos mapping, we showed that BF-projecting neurons in both PrL and IL cortices are robustly recruited by acute and chronic stress. Optogenetic activation of these neurons in the BF increased activity, reduced conditioned freezing, and led to real-time place avoidance, indicating a role in behavioral activation and fear suppression. Subregion-specific manipulations of mPFC revealed a functional dissociation. Selective activation of the IL-BF pathway increased general activity, suppressed freezing during extinction, and produced place preference. In contrast, activation of the PrL-BF projections produced place avoidance without altering activity levels or conditioned fear responses. Anatomical analysis revealed that BF-projecting mPFC neurons represent a heterogenous population that may express CaMKIIa as well as different calcium-binding proteins, while some of their axonal terminals in the BF contain VGluT2 or are located in close apposition to PSD95-positive postsynaptic puncta. The majority of the postsynaptic targets were hDlx-expressing inhibitory neurons in the ventral pallidum. Together, these findings identify the BF as a key target in prefrontal control of affective functions, through which PrL and IL projections differentially regulate motivational state, valence processing, and fear memory. Significance Statement The medial prefrontal cortex (mPFC) exerts top-down control over affective behaviors through subcortical projections, with distinct subregions often mediating opposing or complementary functions. We identify the basal forebrain (BF) as a critical mPFC target through which prelimbic (PrL) and infralimbic (IL) glutamatergic projections exert dissociable effects. IL inputs to the BF, which mainly target inhibitory neurons in the ventral pallidum, promote behavioral activation, suppress fear expression, and produce place preference, reflecting positive valence. In contrast, the PrL to BF pathway, which exhibits comparatively sparse innervation, conveys aversive signals and drives behavioral avoidance. These findings reveal a novel circuit mechanism by which medial prefrontal subregions differentially regulate motivational state, valence processing, and fear memory.

Prescribed-time convergent PD-type adaptive fault-tolerant iterative learning control for nonlinearly parameterized systems with actuator faults

A hybrid system enables plasmid copy number control in yeast

Light‐Induced Alternating Catalysis on Single‐Atom Ruthenium Embedded in Covalent Organic Frameworks for High‐Performance Photo‐Assisted Li–O ₂ Batteries

ABSTRACT The development of high‐efficiency cathode catalysts is crucial for advancing photo‐assisted non‐aqueous lithium–oxygen (Li–O 2 ) batteries, which leverage solar energy to reduce the high overpotential for driving oxygen reduction and evolution processes. However, the state‐of‐the‐art photo‐cathode catalysts often lack multi‐step conversion pathways that regulate interactions between complex active sites and reactive oxygen‐related intermediates within Li–O 2 battery systems. Herein, we report a new light‐induced alternating catalytic mechanism based on a single‐atom Ru‐embedded covalent organic framework assembled from a triazine‐core C3‐symmetric node and π‐extended perylene‐diimide linkers (T‐PDI), generating an ordered conjugated Ru/T‐PDI network that functions as a high‐performance photo cathode of the Li–O 2 battery. Unlike conventional photo‐assisted catalysts that operate through the single‐site activity, the Ru/T‐PDI electrode enables dynamic migration and efficient conversion of reactive oxygen species between catalytic sites across multiple selective sites. This mechanism orchestrates the multi‐step transformation process within Li–O 2 batteries, significantly enhancing catalytic efficiency of active sites and facilitating both the formation and decomposition of Li 2 O 2 products. As a result, the photo‐assisted Li–O 2 battery employing the Ru/T‐PDI cathode achieves a quite low overpotential, outstanding cycling stability and excellent rate performance. This work provides crucial insights for reaction mechanism studies and catalyst design for next‐generation light‐driven metal–oxygen batteries.

Distinct neural modes carry information about attempted grasp timing and force in the sensorimotor cortex

Humans perform a variety of complex hand movements to manipulate objects, requiring precise control of changing forces. Understanding the role of sensorimotor cortex and the cortical dynamics underlying these actions is crucial for developing interventions that restore dexterous hand function after injury or disease. In this study, two male individuals with tetraplegia resulting from cervical spinal cord injury attempted a series of isometric grasps. Neural activity was recorded from the motor and somatosensory cortices using intracortical microelectrode arrays while participants attempted to exert a static or ramping force up and down. Despite their inability to execute movement and limited afferent input, the spiking activity in motor and somatosensory cortex was modulated with the task. Within the neural response we identified independent neural modes - distinct patterns of population-level neural activity that were informative about both the timing and magnitude of the attempted force. Moreover, distinct neural modes were observed during static and dynamic grasping conditions, suggesting independent control schemes for maintaining and changing forces. These modes were related to phases of the task, including the onset, offset, holding periods, as well as increasing and decreasing attempted forces. These results will inform the design of intracortical brain-computer interface (iBCI) systems that can leverage the patterns of grasp and force control evident in sensorimotor cortex during attempted movement to restore dexterous hand function. Significance Statement Restoring dexterous hand function after injury remains a major challenge, partly due to an incomplete understanding of the cortical dynamics underlying grasping and force control. In this study, we investigated neural activity within the motor and somatosensory cortices of individuals with tetraplegia attempting to perform grasps to different target forces with varying temporal profiles. We identified distinct neural modes modulated during specific phases of grasp that encode attempted force information throughout the task. These findings suggest that brain-computer interfaces could leverage these neural modes to restore grasping and force modulation.

Instrument-dependent variability affects both microplastic polymer identification and quantification: an inter-laboratory comparison using polymer standards

Abstract Microplastic analysis is a critical tool for environmental risk assessments and policy development, aligning with several UN Sustainability Goals, however the extent to which analytical outcomes depend on instrument type and spectral reference libraries remains poorly quantified. Here, we present an inter-laboratory comparison study across seven countries evaluating both infrared polymer identification and fluorescent microscopy quantification, using pristine individual polymer standards, mixed polymer standards, and controlled recovery experiments. Participants used standardised protocols and reference materials, differing only in instrument manufacturer, type, reference library, and observer. Our results demonstrate substantial inter-laboratory variability in spectra match quality, polymer identification accuracy, polymer composition in mixed samples, and recovery rates from standardised matrices. Our findings highlight strong instrument- and library-dependent effects on data output despite the implementation of standardised protocols. Collectively, our findings demonstrate that protocol standardisation alone is insufficient to ensure inter-laboratory comparability and that substantial uncertainty persists in reported microplastic composition and abundance. We therefore propose a collaborative approach between researchers and instrument manufacturers encompassing library harmonisation, instrument calibration, and transparent reporting. Without such measures, reported microplastic composition and abundance may continue to reflect laboratory-specific artefacts rather than true environmental variability, ultimately limiting the confidence and policy impact of the reported results.

Human cortex organizes dynamic co-fluctuations along the sensorimotor-association axis

Engineering Surface Hydroxyls of Zeolites to Suppress Sintering of Confined PtSn Clusters for Stable Propane Dehydrogenation

ABSTRACT Propane dehydrogenation (PDH) is an attractive on‐purpose route for propylene production, yet catalyst deactivation under harsh hydrogen‐free conditions remains a major challenge. Although zeolite confinement can stabilize PtSn active sites, gradual sintering during long‐term operation at high temperatures persists. Here we developed an HF‐free post‐synthetic silylation strategy using hexamethyldisilazane (HMDS) to selectively passivate surface silanols in silicalite‐1 zeolites to enhance the stability of encapsulated Pt 1 Sn 1 alloy clusters. The resulting catalyst maintains stable PDH performance during a directly measured 2160 h on‐stream test under hydrogen‐free and pure C 3 H 8 conditions at 550°C. Post‐reaction characterizations demonstrate that the enhanced stability originates from the effective suppression of PtSn sintering under reaction conditions, with the PtSn alloy clusters retaining an average size of only 1.0 ± 0.2 nm after 2160 h on stream. This remarkable sintering resistance is attributed to the passivation of external‐surface and pore‐mouth silanols, which eliminates the hydroxyl anchoring and nucleation sites that would otherwise capture outward‐migrating PtSn species and promote their nucleation and coalescence on the external zeolite surface. These findings identify post‐synthetic hydroxyl passivation as a practical strategy to reinforce zeolite confinement and stabilize sub‐nanometer bimetallic clusters for high‐temperature dehydrogenation.

Spatial Preference-Weighted Representation of Multiple Stimuli in Cortical Area MT

Segregating objects from one another and the background is essential for perception. In natural scenes, it is common to encounter spatially separated stimuli, such as distinct figure-ground regions, adjacent objects, and partial occlusions. Neurons in mid- and high-level visual cortex have large receptive fields (RFs) that often encompass multiple, spatially separated stimuli. It is unclear how neurons represent and segregate multiple stimuli within their RFs, and the role of spatial cues. We recorded neuronal responses in the middle-temporal (MT) cortex of male rhesus macaques to spatially separated random-dot stimuli that moved simultaneously in two directions. We found that across motion directions, responses to bidirectional stimuli were systematically biased toward the component located at the neuron’s preferred RF subregion. The sign and magnitude of this spatial-location bias were predicted by the neuron’s spatial preference for single stimuli presented in isolation. The bias persisted when attention was directed away from the RF, changed predictably when the motion border was shifted within the RF, and developed over time, indicating a stimulus-driven spatial weighting mechanism. Bidirectional responses were well described by a spatial preference-weighted normalization model, in which the responses elicited by individual components are weighted and combined according to the neuron’s spatial preference. Bidirectional stimuli also reduced model-inferred gain variability, suggesting potential engagement of response-stabilizing mechanisms. These results show that MT neurons capitalize on RF spatial selectivity to represent multiple motion components. Across a neuron population with diverse spatial preferences, this coding strategy provides a neural substrate for segregating spatially separated moving stimuli. Significance Statement Elucidating how neurons represent multiple visual stimuli is essential for understanding neural coding in natural scenes. We found that MT neurons do not simply average spatially separated motion components within their RFs. Instead, small spatial preferences measured with single stimuli were amplified into substantial spatial biases when two stimuli were presented together, causing neurons to preferentially represent the component at their preferred RF subregion. This response pattern was captured by a spatial preference-weighted normalization model, extending the normalization framework by showing that RF spatial selectivity determines how multiple motion signals are weighted. A possible circuit implementation further suggests how spatially selective inputs, broad direction pooling, and divisive normalization could support segregation of spatially separated moving stimuli.

Adaptive spatiotemporal feature fusion attention-enhanced ConvLSTM for smart meter lifespan assessment

Insights into the mechanisms of NH3 inhibition on Cu-CHA SCR catalysts

Abstract Ammonia (NH 3 ) inhibition during the selective catalytic reduction (SCR) of nitrogen oxides (NO x ) over Cu-exchanged chabazite (Cu-CHA) catalysts limits low-temperature performance, yet its molecular origin remains unclear. Here we show that excess NH 3 selectively suppresses the oxidation half-cycle of the SCR reaction while leaving the reduction half-cycle largely unaffected. By combining kinetic measurements, operando electron paramagnetic resonance spectroscopy, and density functional theory calculations, we identify hindered mobility of Cu + ions as the key factor. Specifically, NH 3 coordination increases the energy barrier for Cu + diffusion, preventing the formation of reactive Cu 2+ -oxo dimer intermediates required for efficient oxidation. Spectroscopic measurements further reveal that the extent of inhibition depends strongly on temperature and copper loading. These insights provide a mechanistic basis for mitigating NH 3 inhibition, suggesting that improved catalyst design and optimized operating conditions can enhance low-temperature SCR performance in practical emission control systems.

Selective and Potent First‐in‐Class CRBN‐Dependent Molecular Glue Degraders of WW Domain‐Binding Protein 4

ABSTRACT Targeted protein degradation via molecular glues represents a powerful modality for modulating “undruggable” proteins. Herein, through proteomic profiling of a CRBN‐binding library and rigorous structure‐activity relationship (SAR) refinement, we report the discovery of dWBP4‐1: a first‐in‐class, highly selective, CRBN‐dependent molecular glue degrader of the spliceosome‐associated scaffold protein WBP4. dWBP4‐1 induces rapid, nanomolar degradation of WBP4 via a canonical G‐loop‐mediated mechanism, exhibiting exceptional proteome‐wide selectivity with negligible transcriptomic or alternative splicing perturbation. Leveraging this highly specific target‐glue interaction, we mapped the minimal WBP4 degron to a 41‐amino‐acid sequence to establish a compact, inducible chemical‐genetic platform termed wTAG. When fused to diverse proteins of interest, wTAG enables robust, monotonic degradation devoid of the hook effect. While the wTAG system is highly versatile, we delineate its boundaries when applied to challenging targets like Cyclin D1, where factors such as steric hindrance, lysine availability, complex sequestration, and tag accessibility (N‐ vs. C‐terminal fusion) must be carefully interrogated. Collectively, this study highlights the discovery of a highly selective WBP4 molecular glue and translates its underlying degron into a robust tool for precise protein control.

Opposing control of the respiratory brainstem on multiple timescales achieved by noradrenaline and glutamate release from the locus coeruleus

The locus coeruleus (LC) provides widespread noradrenergic (NAergic) modulation throughout the brain to influence a wide range of functions, including breathing. Although both anatomical and physiological evidence supports the involvement of the LC in both the upstream integration and the downstream modulation of breathing, the circuitry behind the latter is unknown. Here, we show that LC neurons in adult male and female mice send projections to the Kӧlliker-Fuse nucleus (KF), a critical site in the control of breathing. Long duration activation of LC neuron terminals in pontine slices induces persistent inhibitory and excitatory NA currents or increases firing rate in postsynaptic KF neurons. Short stimulation on the other hand leads to VGluT2-dependent rapid release of glutamate that may co-occur with slower NAergic transmission in a monosynaptic circuit. Together these results demonstrate that LC neurons can exert flexible, opposing effects on different timescales via glutamatergic and NAergic signaling onto a key respiratory brainstem nucleus. Significance Statement The ability for the LC to co-release fast-acting neurotransmitters and slower-acting neuromodulators provides an increased capacity to differentially and flexibly modulate downstream targets to coordinate cognitive and autonomic functions including breathing, stress and arousal. Here, we demonstrate that LC neurons may co-release glutamate and noradrenaline onto the Kӧlliker-Fuse nucleus (KF), a critical respiratory center, enabling rapid excitation via glutamate and slower opposing modulation via α1- and α2-adrenergic receptors. This multiplexing mechanism may allow the LC to dynamically adjust breathing during diverse behavioral states, stress, or metabolic demand through a single anatomical pathway. Understanding this neuromodulatory gateway has implications for respiratory disorders where LC function is compromised and provides a conserved circuit model for studies on the state-dependent control of breathing.

SE-HG-GNN: a novel explainable deep learning approach for financial distress prediction using optimized graph neural networks

The accumulation of methylglyoxal and acrolein impairs arginine homeostasis causing hyperglycemia and renal abnormalities in male zebrafish

Abstract Reactive carbonyl species contribute to diabetes and its complications, but how the interconnections of carbonyl-detoxifying enzymes regulate metabolic homeostasis through arginine metabolism remains unclear. Here we generate zebrafish lacking both glyoxalase 1 and aldo-keto reductase 1A1A, two major enzymes that detoxify methylglyoxal and acrolein. Double deficiency causes carbonyl accumulation, suppresses arginine metabolism, and impairs insulin signaling, resulting in elevated glucose levels in larvae and in postprandial hyperglycemia in adult male zebrafish. These metabolic alterations are accompanied by glomerular basement membrane thickening and podocyte effacement, whereas retinal vasculature remains unaffected. Arginine supplementation restores Akt phosphorylation, improves insulin signaling, and attenuates renal pathology, indicating that disrupted arginine metabolism mediates the metabolic consequences of carbonyl stress. Our findings identify glyoxalase 1 and aldo-keto reductase 1A1A as cooperative regulators of carbonyl detoxification and reveal a carbonyl–arginine axis linking reactive carbonyl accumulation to impaired insulin signaling, hyperglycemia, and tissue-specific diabetic injury.

Regulating Electrolyte Microstructure via Anion‐Solvent Coordination Enables Fast Interfacial Kinetics Toward Practical Zinc Pouch Cells

ABSTRACT Solvation structure regulation plays crucial roles in stabilizing the Zn anode by suppressing dendrite and hydrogen evolution, but sluggish ion transport results in poor rate performance of the anode. In this study, we proposed an “anion regulation” strategy by introducing amphiphilic benzyl alcohol (BA) to the Zn(OTf) 2 electrolyte, which modulated the electrolyte microstructure and dual solvation structure. BA provided weak solvation ability with Zn 2+ and induced the Zn 2+ ‐OTf–BA dual solvation structure by anion‐solvent interaction, which downsized the solvation clusters with improved microscopic uniformity, improving the Zn 2+ diffusion kinetics. Synergistic regulation on the first solvation shell was also achieved, where BA not only reduced the coordinated water but also weakened the Zn 2+ ‐OTf − interaction, accelerating the desolvation kinetics. Additionally, an inorganic‐rich solid electrolyte interphase was constructed by anion decomposition, favorable for interfacial stability. Consequently, the modulated electrolyte enabled the Zn anode with impressive rate performance (1500 h, 10 mA cm −2 /10 mAh cm −2 ; 294 h, 20 mA cm −2 /20 mAh cm −2 ) and superior stability at 85% utilization (260 h). The 1.2 Ah Zn‐NH 4 V 4 O 10 pouch cell also maintained cyclability (∼85.3% retention) over 200 cycles. This work provides a novel way of regulating the electrolyte microstructure to improve interfacial kinetics toward practical zinc‐ion batteries.

AAV-mediated overexpression of Prdm12 in knee-innervating afferents reduces inflammatory joint pain and neuronal hyperexcitability in female mice

Inflammatory joint pain features in numerous musculoskeletal disorders that affect millions globally. The Prdm12 gene encodes a conserved zinc finger transcriptional regulator expressed selectively in the nervous system. In humans, PRDM12 mutations can cause congenital insensitivity to pain (CIP) or midface toddler excoriation syndrome (MiTES). Prdm12 is prominently expressed in developing somatosensory ganglia, where it plays a crucial role in nociceptive neuron development, its expression being maintained in mature C-LTMRs (C-low threshold mechanoreceptors) and nociceptive neurons. Despite enhanced understanding of Prdm12’s role in neuronal excitability and pain behavior, the impact of Prdm12 overexpression in mature nociceptive neurons has not been explored. Here, we conducted intravenous injection of AAV-PHP.S viral vectors encoding Prdm12-GFP (Prdm12-AAV) or GFP alone (Control-AAV), observing no change in thermal or motor behavior. When examining the properties of Prdm12 overexpressing sensory neurons isolated from male mice, we observed an increase in rheobase alongside decreased neuronal responses to capsaicin and ATP, indicating a decrease in TRPV1 and P2X ion channel activity, respectively. We next conducted intraarticular administration of viral constructs in female mice to determine how Prdm12 overexpression in knee-innervating sensory neurons alters their excitability and influences inflammatory joint pain induced by intraarticular administration of complete Freund’s adjuvant (CFA). Prdm12 overexpression in knee-innervating neurons decreased inflammation-induced changes in digging and weight bearing, prevented inflammation-induced neuronal hyperexcitability, and decreased macroscopic voltage-gated ion channel conductance. Our findings illustrate that Prdm12 overexpression strongly modulates neuronal excitability in adult animals, highlighting its importance in pain perception and its potential as an analgesic target. Significance Statement Chronic joint pain is a major cause of disability worldwide, yet effective treatments remain limited. This study identifies the transcriptional regulator Prdm12 as a key modulator of sensory neuron excitability and inflammatory joint pain in adult mice. Using AAV-mediated gene delivery, we show that Prdm12 overexpression in knee-innervating neurons prevents inflammation-induced neuronal hyperexcitability and reduces pain-related behaviors in female mice. These findings extend Prdm12’s known developmental roles into adulthood and reveal its capacity to suppress nociceptive signaling. Our results suggest that targeted overexpression of Prdm12 activity could represent a novel gene-based strategy for treating chronic inflammatory pain conditions.

A data-driven machine learning model for effective diabetes diagnosis

Single-crystal organic electrode for aqueous proton batteries