Cytidine triphosphate(CTP),as a substance involved in the metabolism of phospholipids,proteins and nucleic acids,has precise drug effects and is a direct precursor for the synthesis of drugs such as citicoline.In this...Cytidine triphosphate(CTP),as a substance involved in the metabolism of phospholipids,proteins and nucleic acids,has precise drug effects and is a direct precursor for the synthesis of drugs such as citicoline.In this study,we established an in vitro six-enzyme cascade system to generate CTP.To avoid thermodynamic bottlenecks,we employed a circuitous and two-stage reaction strategy.Using cytidine as the key substrate,the final product CTP is obtained via the deamination and uridine phosphorylation pathways,relying on the irreversible reaction of cytidine triphosphate synthase to catalyze the amination of uridine triphosphate.Several extremophilic microbial-derived deaminases were screened and characterized,and a suitable cytidine deaminase was selected to match the first-stage reaction conditions.In addition,directed evolution modification of the rate-limiting enzyme CTP synthetase in the pathway yielded a variant that successfully relieved the product feedback inhibition,along with a 1.7-fold increase in activity over the wild type.After optimizing the reaction conditions,we finally carried out the catalytic reaction at an initial cytidine concentration of 20 mM,and the yield of CTP exceeded 82%within 10.0 h.展开更多
Chronic migraine(CM)is a prevalent and highly debilitating neurological disorder.Functional magnetic resonance imaging(fMRI)studies have demonstrated associations between abnormal brain region activation and CM,yet th...Chronic migraine(CM)is a prevalent and highly debilitating neurological disorder.Functional magnetic resonance imaging(fMRI)studies have demonstrated associations between abnormal brain region activation and CM,yet the underlying complex neural circuitry mechanisms remain unclear.The spinal trigeminal nucleus caudalis(Sp5C)serves as the primary central hub for orofacial nociceptive input,receiving trigeminal pain signals and projecting to higher-order centers such as the thalamus.Therefore,we sought to investigate whether the Sp5C region and its associated circuits were involved in CM pathogenesis.In this study,we established a CM mouse model through repeated intraperitoneal injections of nitroglycerin(NTG).Using a combination of in vivo fiber photometry and in vitro c-Fos immunohistochemistry,we found a marked periorbital and plantar mechanical allodynia in CM mice,accompanied by increased glutamatergic neuronal activity in Sp5C.Chemogenetic manipulation of Sp5C glutamatergic neurons(Sp5CV^(glut2))bidirectionally modulated migraine-like behaviors and induced pain-related affective states,as evidenced by conditioned place preference/aversion(CPP/CPA)paradigms.Anterograde viral tracing revealed dense projections from Sp5C^(Vglut2)to the subthalamic nucleus(STN),which was activated in CM mice.Optogenetic activation of the Sp5C-STN pathway similarly produced migraine-like behaviors and pain-related aversive memory in mice.Altogether,we revealed a critical role of the Sp5CVglut2-STN circuit in the development and modulation of CM.Our findings provide novel mechanistic insights into the central mechanisms underlying CM,establishing potential theoretical foundations for clinical diagnosis and therapeutic development.展开更多
After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the tim...After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.展开更多
In this paper,we present a circuit model of single-quantum-well InGaN/GaN light-emitting diodes based on the standard rate equations.Two rate equations describe carrier transport processes occurring in sep-arate confi...In this paper,we present a circuit model of single-quantum-well InGaN/GaN light-emitting diodes based on the standard rate equations.Two rate equations describe carrier transport processes occurring in sep-arate confinement heterostructure and quantum well respectively,and the third equation describes the varied photons in quantum well.By using the presented model,impacts of quantum well thickness on the static and dynamic performances are investigated.Simulated results show that LED with 4 nm well exhibits better lightcurrent(L-I)performance,but LED with 3 nm well presents wider 3 dB modulation bandwidth.It reveals that high carrier density in quantum well is detrimental to the static performance,but beneficial to the dynamic performance.展开更多
Epilepsy,a common neurological disorder,is characterized by recurrent seizures that can lead to cognitive,psychological,and neurobiological consequences.The pathogenesis of epilepsy involves neuronal dysfunction at th...Epilepsy,a common neurological disorder,is characterized by recurrent seizures that can lead to cognitive,psychological,and neurobiological consequences.The pathogenesis of epilepsy involves neuronal dysfunction at the molecular,cellular,and neural circuit levels.Abnormal molecular signaling pathways or dysfunction of specific cell types can lead to epilepsy by disrupting the normal functioning of neural circuits.The continuous emergence of new technologies and the rapid advancement of existing ones have facilitated the discovery and comprehensive understanding of the neural circuit mechanisms underlying epilepsy.Therefore,this review aims to investigate the current understanding of the neural circuit mechanisms in epilepsy based on various technologies,including electroencephalography,magnetic resonance imaging,optogenetics,chemogenetics,deep brain stimulation,and brain-computer interfaces.Additionally,this review discusses these mechanisms from three perspectives:structural,synaptic,and transmitter circuits.The findings reveal that the neural circuit mechanisms of epilepsy encompass information transmission among different structures,interactions within the same structure,and the maintenance of homeostasis at the cellular,synaptic,and neurotransmitter levels.These findings offer new insights for investigating the pathophysiological mechanisms of epilepsy and enhancing its clinical diagnosis and treatment.展开更多
Replicating the chaotic characteristics inherent in nonlinear dynamical systems via machine learning(ML)is a key challenge in this rapidly advancing interdisciplinary field.In this work,we explore the potential of var...Replicating the chaotic characteristics inherent in nonlinear dynamical systems via machine learning(ML)is a key challenge in this rapidly advancing interdisciplinary field.In this work,we explore the potential of variational quantum circuits(VQC)for learning the stochastic properties of classical nonlinear dynamical systems.Specifically,we focus on the one-and two-dimensional logistic maps,which,while simple,remain under-explored in the context of learning dynamical characteristics.Our findings reveal that,even for such simple dynamical systems,accurately replicating longterm characteristics is hindered by a pronounced sensitivity to overfitting.While increasing the parameter complexity of the ML model typically enhances short-term prediction accuracy,it also leads to a degradation in the model’s ability to replicate long-term characteristics,primarily due to the detrimental effects of overfitting on generalization power.By comparing the VQC with two widely recognized classical ML techniques,which are long short-term memory(LSTM)networks for timeseries processing and reservoir computing,we demonstrate that VQC outperforms these methods in terms of replicating long-term characteristics.Our results suggest that for the ML of dynamics,it is demanded to develop more compact and efficient models(such as VQC)rather than more complicated and large-scale ones.展开更多
Kesterite Cu_(2)ZnSn(S,Se)_(4)(CZTSSe)solar cells suffer from significant open-circuit voltage(V_(OC))deficits due to severe interfacial and bulk recombination,restricting their power conversion efficiency(PCE)far bel...Kesterite Cu_(2)ZnSn(S,Se)_(4)(CZTSSe)solar cells suffer from significant open-circuit voltage(V_(OC))deficits due to severe interfacial and bulk recombination,restricting their power conversion efficiency(PCE)far below the ShockleyQueisser limit.This work proposes a low-temperature annealing strategy during ITO sputtering(SA)to synergistically address these challenges.The temperature applied during ITO sputtering not only improves the crystallinity,carrier concentration,and optical transmittance of the ITO layer but also promotes the diffusion of In from ITO into both CdS and CZTSSe layers.Consequently,lattice matching at the CZTSSe/CdS interface is optimized,enabling epitaxial growth.And a favorable ITO/In:CdS/In&Cd:CZTSSe structure with optimal band alignment is obtained.As a result,a champion device with a PCE of 1_(4).29%was achieved.The SA-treating also enabled the CZTSSe solar cells to achieve the highest V_(OC)reported to date,exceeding 590 mV.This underscores the essential role of SA processing in optimizing interface engineering and suppressing defects,thus promoting the development of low-cost,high-performance kesterite photovoltaics.展开更多
Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after inju...Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.展开更多
Classical computation of electronic properties in large-scale materials remains challenging.Quantum computation has the potential to offer advantages in memory footprint and computational scaling.However,general and v...Classical computation of electronic properties in large-scale materials remains challenging.Quantum computation has the potential to offer advantages in memory footprint and computational scaling.However,general and viable quantum algorithms for simulating large-scale materials are still limited.We propose and implement random-state quantum algorithms to calculate electronic-structure properties of real materials.Using a random state circuit on a small number of qubits,we employ real-time evolution with first-order Trotter decomposition and Hadamard test to obtain electronic density of states,and we develop a modified quantum phase estimation algorithm to calculate real-space local density of states via direct quantum measurements.Furthermore,we validate these algorithms by numerically computing the density of states and spatial distributions of electronic states in graphene,twisted bilayer graphene quasicrystals,and fractal lattices,covering system sizes from hundreds to thousands of atoms.Our results manifest that the random-state quantum algorithms provide a general and qubit-efficient route to scalable simulations of electronic properties in large-scale periodic and aperiodic materials.展开更多
Superconducting diodes,which enable dissipationless supercurrent flow in one direction while blocking it in the reverse direction,are emerging as pivotal components for superconducting electronics.The development of e...Superconducting diodes,which enable dissipationless supercurrent flow in one direction while blocking it in the reverse direction,are emerging as pivotal components for superconducting electronics.The development of editable superconducting diodes could unlock transformative applications,including dynamically reconfigurable quantum circuits that adapt to operational requirements.Here,we report the first observation of the superconducting diode effect(SDE)in LaAlO_(3)/KTaO_(3) heterostructures—a two-dimensional oxide interface superconductor with exceptional tunability.We observe a strong SDE in Hall-bar(or strip-shaped)devices under perpendicular magnetic fields(<15 Oe),with efficiencies above 40%and rectification signals exceeding 10 mV.Through conductive atomic force microscope lithography,we demonstrate reversible nanoscale editing of the SDE’s polarity and efficiency by locally modifying the superconducting channel edges.This approach enables multiple nonvolatile configurations within a single device,realizing an editable superconducting diode.Our work establishes LaAlO_(3)/KTaO_(3) as a platform for vortex-based nonreciprocal transport and provides a pathway toward designer quantum circuits with on-demand functionalities.展开更多
Oligodendrocyte precursor cells(OPCs)tile the central nervous system ubiquitously,accounting for about 5%of the total cell population in the central nervous system.Beyond their role in myelination,OPCs actively shape ...Oligodendrocyte precursor cells(OPCs)tile the central nervous system ubiquitously,accounting for about 5%of the total cell population in the central nervous system.Beyond their role in myelination,OPCs actively shape neural circuits(Fang and Bai,2023),by releasing neuromodulators,pruning synapses,maintaining the homeostasis of extracellular potassium concentration,and interacting with endothelial cells.展开更多
Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these...Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.展开更多
Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairme...Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.展开更多
The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency i...The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.展开更多
Depressive disorder is a chronic,recurring,and potentially life-endangering neuropsychiatric disease.According to a report by the World Health Organization,the global population suffering from depression is experienci...Depressive disorder is a chronic,recurring,and potentially life-endangering neuropsychiatric disease.According to a report by the World Health Organization,the global population suffering from depression is experiencing a significant annual increase.Despite its prevalence and considerable impact on people,little is known about its pathogenesis.One major reason is the scarcity of reliable animal models due to the absence of consensus on the pathology and etiology of depression.Furthermore,the neural circuit mechanism of depression induced by various factors is particularly complex.Considering the variability in depressive behavior patterns and neurobiological mechanisms among different animal models of depression,a comparison between the neural circuits of depression induced by various factors is essential for its treatment.In this review,we mainly summarize the most widely used behavioral animal models and neural circuits under different triggers of depression,aiming to provide a theoretical basis for depression prevention.展开更多
Ecological security provides the basis of maintaining both a sustainable regional ecosystem and economic development.However,few studies have focused on how the features such as topography and geomorphology,lithologic...Ecological security provides the basis of maintaining both a sustainable regional ecosystem and economic development.However,few studies have focused on how the features such as topography and geomorphology,lithologic stratigraphic assemblages,and geohazard distribution affect the construction of ecological security patterns and the layout of optimization measures.In order to comprehensively reveal the key areas and key objects of ecological restoration in karst basins,this study takes the Beipan River Basin(BRB)as an example,constructs an ecological security pattern(ESP)based on the methods of morphological spatial pattern analysis(MSPA),landscape connectivity analysis and circuit theory,and lays out the optimization measures in combination with the spatial distribution characteristics of topographic and geomorphological differences and lithological stratigraphic combinations.The results show that 151 ecological sources,343 ecological corridors,121 pinch points and 178 barriers constitute the ESP of the BRB.Lithology is closely related to the spatial distribution characteristics of ecological source sites.Level 1 and 2 ecological sources(The ecological sources were categorized into level 1,level 2,and level 3 source from high to low importance.)are concentrated in the Emeishan basalt region of the upstream and the clastic and impure carbonate rock region of the downstream part of the BRB;level 3ecological sources are concentrated in the carbonate rock region of the midstream.Taking into account the outstanding ecological problems in the basin,and based on the characteristics of lithology and geohazard distribution,we propose the optimization scheme of“three axes,three zones and multiple points”for the ESP and the layout of specific measures of the BRB.The results can provide scientific references for maintaining ecological security maintenance in karst ecologically fragile areas.展开更多
Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse functi...Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse function.We have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine morphogenesis.To investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing chow.We found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection neurons.These findings are further corroborated by increased synaptic activity and transient generation of immature silent synapses.Prolonged MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and connectivity.Our data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult brain.These findings may have implications for regenerative therapy in aging and neurodegeneration conditions.展开更多
In the 9 December 2024 issue of Nature[1],a team of Google engineers reported breakthrough results using“Willow”,their lat-est quantum computing chip(Fig.1).By meeting a milestone“below threshold”reduction in the ...In the 9 December 2024 issue of Nature[1],a team of Google engineers reported breakthrough results using“Willow”,their lat-est quantum computing chip(Fig.1).By meeting a milestone“below threshold”reduction in the rate of errors that plague super-conducting circuit-based quantum computing systems(Fig.2),the work moves the field another step towards its promised super-charged applications,albeit likely still many years away.Areas expected to benefit from quantum computing include,among others,drug discovery,materials science,finance,cybersecurity,and machine learning.展开更多
The rise of large-scale artificial intelligence(AI)models,such as ChatGPT,Deep-Seek,and autonomous vehicle systems,has significantly advanced the boundaries of AI,enabling highly complex tasks in natural language proc...The rise of large-scale artificial intelligence(AI)models,such as ChatGPT,Deep-Seek,and autonomous vehicle systems,has significantly advanced the boundaries of AI,enabling highly complex tasks in natural language processing,image recognition,and real-time decisionmaking.However,these models demand immense computational power and are often centralized,relying on cloud-based architectures with inherent limitations in latency,privacy,and energy efficiency.To address these challenges and bring AI closer to real-world applications,such as wearable health monitoring,robotics,and immersive virtual environments,innovative hardware solutions are urgently needed.This work introduces a near-sensor edge computing(NSEC)system,built on a bilayer AlN/Si waveguide platform,to provide real-time,energy-efficient AI capabilities at the edge.Leveraging the electro-optic properties of AlN microring resonators for photonic feature extraction,coupled with Si-based thermo-optic Mach-Zehnder interferometers for neural network computations,the system represents a transformative approach to AI hardware design.Demonstrated through multimodal gesture and gait analysis,the NSEC system achieves high classification accuracies of 96.77%for gestures and 98.31%for gaits,ultra-low latency(<10 ns),and minimal energy consumption(<0.34 pJ).This groundbreaking system bridges the gap between AI models and real-world applications,enabling efficient,privacy-preserving AI solutions for healthcare,robotics,and next-generation human-machine interfaces,marking a pivotal advancement in edge computing and AI deployment.展开更多
In a pulsed plasma thruster,the voltage distribution between the electrodes is a key factor that influences the ionization process.However,few researchers have conducted in-depth studies of this phenomenon in the past...In a pulsed plasma thruster,the voltage distribution between the electrodes is a key factor that influences the ionization process.However,few researchers have conducted in-depth studies of this phenomenon in the past.Reported here are measurements of the voltage distribution between the plates of a parallel-plate pulsed plasma thruster under different discharge voltages,based on which the variations in the total circuit inductance and resistance as well as those between the plates are calculated.The results show that the time-averaged voltage across the plates accounts for 28.7%-50.4%of the capacitor voltage.As the capacitor initial voltage increases from 1250 V to 2000 V,the voltage across the plates rises,but its proportion relative to the capacitor voltage decreases.For every 250 V increase in the capacitor initial voltage,the average voltage proportion across the plates decreases by approximately 2%-3%.Additionally,the voltage proportion decreases gradually from the end near the propellant outward.The voltage distribution ratio between the plates is correlated with the proportions of the resistance and inductance between the plates relative to the total circuit.展开更多
基金supported by the National Key Research and Development Program of China(2022YFC3401700)the National Natural Science Foundation of China(Grant No.32171478)the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(Grant No.TSBICIP-KJGG-009).
文摘Cytidine triphosphate(CTP),as a substance involved in the metabolism of phospholipids,proteins and nucleic acids,has precise drug effects and is a direct precursor for the synthesis of drugs such as citicoline.In this study,we established an in vitro six-enzyme cascade system to generate CTP.To avoid thermodynamic bottlenecks,we employed a circuitous and two-stage reaction strategy.Using cytidine as the key substrate,the final product CTP is obtained via the deamination and uridine phosphorylation pathways,relying on the irreversible reaction of cytidine triphosphate synthase to catalyze the amination of uridine triphosphate.Several extremophilic microbial-derived deaminases were screened and characterized,and a suitable cytidine deaminase was selected to match the first-stage reaction conditions.In addition,directed evolution modification of the rate-limiting enzyme CTP synthetase in the pathway yielded a variant that successfully relieved the product feedback inhibition,along with a 1.7-fold increase in activity over the wild type.After optimizing the reaction conditions,we finally carried out the catalytic reaction at an initial cytidine concentration of 20 mM,and the yield of CTP exceeded 82%within 10.0 h.
基金supported by the National Natural Science Foundation of China(No.32571336 and 32271048)Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM(No.2025IHM01100)。
文摘Chronic migraine(CM)is a prevalent and highly debilitating neurological disorder.Functional magnetic resonance imaging(fMRI)studies have demonstrated associations between abnormal brain region activation and CM,yet the underlying complex neural circuitry mechanisms remain unclear.The spinal trigeminal nucleus caudalis(Sp5C)serves as the primary central hub for orofacial nociceptive input,receiving trigeminal pain signals and projecting to higher-order centers such as the thalamus.Therefore,we sought to investigate whether the Sp5C region and its associated circuits were involved in CM pathogenesis.In this study,we established a CM mouse model through repeated intraperitoneal injections of nitroglycerin(NTG).Using a combination of in vivo fiber photometry and in vitro c-Fos immunohistochemistry,we found a marked periorbital and plantar mechanical allodynia in CM mice,accompanied by increased glutamatergic neuronal activity in Sp5C.Chemogenetic manipulation of Sp5C glutamatergic neurons(Sp5CV^(glut2))bidirectionally modulated migraine-like behaviors and induced pain-related affective states,as evidenced by conditioned place preference/aversion(CPP/CPA)paradigms.Anterograde viral tracing revealed dense projections from Sp5C^(Vglut2)to the subthalamic nucleus(STN),which was activated in CM mice.Optogenetic activation of the Sp5C-STN pathway similarly produced migraine-like behaviors and pain-related aversive memory in mice.Altogether,we revealed a critical role of the Sp5CVglut2-STN circuit in the development and modulation of CM.Our findings provide novel mechanistic insights into the central mechanisms underlying CM,establishing potential theoretical foundations for clinical diagnosis and therapeutic development.
基金supported by the National Key Research and Development Program of China,No.2023YFC3603705(to DX)the National Natural Science Foundation of China,No.82302866(to YZ).
文摘After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.
文摘In this paper,we present a circuit model of single-quantum-well InGaN/GaN light-emitting diodes based on the standard rate equations.Two rate equations describe carrier transport processes occurring in sep-arate confinement heterostructure and quantum well respectively,and the third equation describes the varied photons in quantum well.By using the presented model,impacts of quantum well thickness on the static and dynamic performances are investigated.Simulated results show that LED with 4 nm well exhibits better lightcurrent(L-I)performance,but LED with 3 nm well presents wider 3 dB modulation bandwidth.It reveals that high carrier density in quantum well is detrimental to the static performance,but beneficial to the dynamic performance.
基金supported by Basic Research Programs of Science and Technology Commission Foundation of Shanxi Province,No.20210302123486(to WJ).
文摘Epilepsy,a common neurological disorder,is characterized by recurrent seizures that can lead to cognitive,psychological,and neurobiological consequences.The pathogenesis of epilepsy involves neuronal dysfunction at the molecular,cellular,and neural circuit levels.Abnormal molecular signaling pathways or dysfunction of specific cell types can lead to epilepsy by disrupting the normal functioning of neural circuits.The continuous emergence of new technologies and the rapid advancement of existing ones have facilitated the discovery and comprehensive understanding of the neural circuit mechanisms underlying epilepsy.Therefore,this review aims to investigate the current understanding of the neural circuit mechanisms in epilepsy based on various technologies,including electroencephalography,magnetic resonance imaging,optogenetics,chemogenetics,deep brain stimulation,and brain-computer interfaces.Additionally,this review discusses these mechanisms from three perspectives:structural,synaptic,and transmitter circuits.The findings reveal that the neural circuit mechanisms of epilepsy encompass information transmission among different structures,interactions within the same structure,and the maintenance of homeostasis at the cellular,synaptic,and neurotransmitter levels.These findings offer new insights for investigating the pathophysiological mechanisms of epilepsy and enhancing its clinical diagnosis and treatment.
基金Project supported in part by Beijing Natural Science Foundation(Grant No.1232025)Peng Huanwu Visiting Pro-fessor Program,and Academy for Multidisciplinary Studies,Capital Normal University.
文摘Replicating the chaotic characteristics inherent in nonlinear dynamical systems via machine learning(ML)is a key challenge in this rapidly advancing interdisciplinary field.In this work,we explore the potential of variational quantum circuits(VQC)for learning the stochastic properties of classical nonlinear dynamical systems.Specifically,we focus on the one-and two-dimensional logistic maps,which,while simple,remain under-explored in the context of learning dynamical characteristics.Our findings reveal that,even for such simple dynamical systems,accurately replicating longterm characteristics is hindered by a pronounced sensitivity to overfitting.While increasing the parameter complexity of the ML model typically enhances short-term prediction accuracy,it also leads to a degradation in the model’s ability to replicate long-term characteristics,primarily due to the detrimental effects of overfitting on generalization power.By comparing the VQC with two widely recognized classical ML techniques,which are long short-term memory(LSTM)networks for timeseries processing and reservoir computing,we demonstrate that VQC outperforms these methods in terms of replicating long-term characteristics.Our results suggest that for the ML of dynamics,it is demanded to develop more compact and efficient models(such as VQC)rather than more complicated and large-scale ones.
基金supported by the National Key Research and Development Program of China(2024YFB4205000)the National Natural Science Foundation of China(52525405,62504071,and 52572217)+1 种基金the Natural Science Foundation of Henan Province(252300421255 and242300420313)the Key Research Projects of Higher Education Institutions in Henan Province(24A430003)。
文摘Kesterite Cu_(2)ZnSn(S,Se)_(4)(CZTSSe)solar cells suffer from significant open-circuit voltage(V_(OC))deficits due to severe interfacial and bulk recombination,restricting their power conversion efficiency(PCE)far below the ShockleyQueisser limit.This work proposes a low-temperature annealing strategy during ITO sputtering(SA)to synergistically address these challenges.The temperature applied during ITO sputtering not only improves the crystallinity,carrier concentration,and optical transmittance of the ITO layer but also promotes the diffusion of In from ITO into both CdS and CZTSSe layers.Consequently,lattice matching at the CZTSSe/CdS interface is optimized,enabling epitaxial growth.And a favorable ITO/In:CdS/In&Cd:CZTSSe structure with optimal band alignment is obtained.As a result,a champion device with a PCE of 1_(4).29%was achieved.The SA-treating also enabled the CZTSSe solar cells to achieve the highest V_(OC)reported to date,exceeding 590 mV.This underscores the essential role of SA processing in optimizing interface engineering and suppressing defects,thus promoting the development of low-cost,high-performance kesterite photovoltaics.
文摘Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.
基金supported by the Major Project for the Integration of ScienceEducation and Industry (Grant No.2025ZDZX02)。
文摘Classical computation of electronic properties in large-scale materials remains challenging.Quantum computation has the potential to offer advantages in memory footprint and computational scaling.However,general and viable quantum algorithms for simulating large-scale materials are still limited.We propose and implement random-state quantum algorithms to calculate electronic-structure properties of real materials.Using a random state circuit on a small number of qubits,we employ real-time evolution with first-order Trotter decomposition and Hadamard test to obtain electronic density of states,and we develop a modified quantum phase estimation algorithm to calculate real-space local density of states via direct quantum measurements.Furthermore,we validate these algorithms by numerically computing the density of states and spatial distributions of electronic states in graphene,twisted bilayer graphene quasicrystals,and fractal lattices,covering system sizes from hundreds to thousands of atoms.Our results manifest that the random-state quantum algorithms provide a general and qubit-efficient route to scalable simulations of electronic properties in large-scale periodic and aperiodic materials.
基金supported by the National Key R&D Program of China (Grant No.2023YFA1406400)the National Natural Science Foundation of China (Grant Nos.12534005 and 12325402)。
文摘Superconducting diodes,which enable dissipationless supercurrent flow in one direction while blocking it in the reverse direction,are emerging as pivotal components for superconducting electronics.The development of editable superconducting diodes could unlock transformative applications,including dynamically reconfigurable quantum circuits that adapt to operational requirements.Here,we report the first observation of the superconducting diode effect(SDE)in LaAlO_(3)/KTaO_(3) heterostructures—a two-dimensional oxide interface superconductor with exceptional tunability.We observe a strong SDE in Hall-bar(or strip-shaped)devices under perpendicular magnetic fields(<15 Oe),with efficiencies above 40%and rectification signals exceeding 10 mV.Through conductive atomic force microscope lithography,we demonstrate reversible nanoscale editing of the SDE’s polarity and efficiency by locally modifying the superconducting channel edges.This approach enables multiple nonvolatile configurations within a single device,realizing an editable superconducting diode.Our work establishes LaAlO_(3)/KTaO_(3) as a platform for vortex-based nonreciprocal transport and provides a pathway toward designer quantum circuits with on-demand functionalities.
基金supported by DeutscheForschungsgemeinschaft(BA 8014/1-1 to XB)University of Saarland(NanoBioMed Young Investigatorgrant 2021 to XB,Anschubsfinanzierung2024to XB,HOMFORExzellenz2025 andAnschubsfinanzierung2025 to LPF)the ChinaPharmaceutical University(UndergraduateInternship Program to YZ).
文摘Oligodendrocyte precursor cells(OPCs)tile the central nervous system ubiquitously,accounting for about 5%of the total cell population in the central nervous system.Beyond their role in myelination,OPCs actively shape neural circuits(Fang and Bai,2023),by releasing neuromodulators,pruning synapses,maintaining the homeostasis of extracellular potassium concentration,and interacting with endothelial cells.
基金supported by the Fundamental Research Funds for Central Public Welfare Research Institute,No.2020CZ-5(to WS and GS)the National Natural Science Foundation of China,No.31970970(to JSR)Fundamental Research Funds for the Central Universities,No.YWF-23-YG-QB-010(to JSR)。
文摘Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord injury.
基金supported by the National Natural Science Foundation of China,Nos.82374561(to JD),82174490(to JF)the Medical and Health Science and Technology Program of Zhejiang Province,No.2021RC098(to JD)the Research Project of Zhejiang Chinese Medical University,Nos.2022JKZKTS44(to JD),2022FSYYZZ07(to JF).
文摘Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.
基金supported by the National Natural Science Foundation of China,No.31771143 (to QZ)Shanghai Municipal Science and Technology Major Project,ZJ Lab+1 种基金Shanghai Center for Brain Science and Brain-Inspired Technology,No.2018SHZDZX01 (to LC)Shanghai Zhou Liangfu Medical Development Foundation “Brain Science and Brain Diseases Youth Innovation Program”(to ZQ)。
文摘The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.
基金supported by the Brain&Behavior Research Foundation(30233).
文摘Depressive disorder is a chronic,recurring,and potentially life-endangering neuropsychiatric disease.According to a report by the World Health Organization,the global population suffering from depression is experiencing a significant annual increase.Despite its prevalence and considerable impact on people,little is known about its pathogenesis.One major reason is the scarcity of reliable animal models due to the absence of consensus on the pathology and etiology of depression.Furthermore,the neural circuit mechanism of depression induced by various factors is particularly complex.Considering the variability in depressive behavior patterns and neurobiological mechanisms among different animal models of depression,a comparison between the neural circuits of depression induced by various factors is essential for its treatment.In this review,we mainly summarize the most widely used behavioral animal models and neural circuits under different triggers of depression,aiming to provide a theoretical basis for depression prevention.
基金jointly supported by the Key Project of the Natural Science Foundation of Guizhou Province(No.Qiankehe Jichu-ZK[2023]Zhongdian027)the Project of the Science and Technology Innovation Base Construction of Guizhou Province(No.Qiankehe Zhongyindi[2023]005)Philosophy and Social Science Planning Subjects in Guizhou Province in 2022(No.22GZYB53)。
文摘Ecological security provides the basis of maintaining both a sustainable regional ecosystem and economic development.However,few studies have focused on how the features such as topography and geomorphology,lithologic stratigraphic assemblages,and geohazard distribution affect the construction of ecological security patterns and the layout of optimization measures.In order to comprehensively reveal the key areas and key objects of ecological restoration in karst basins,this study takes the Beipan River Basin(BRB)as an example,constructs an ecological security pattern(ESP)based on the methods of morphological spatial pattern analysis(MSPA),landscape connectivity analysis and circuit theory,and lays out the optimization measures in combination with the spatial distribution characteristics of topographic and geomorphological differences and lithological stratigraphic combinations.The results show that 151 ecological sources,343 ecological corridors,121 pinch points and 178 barriers constitute the ESP of the BRB.Lithology is closely related to the spatial distribution characteristics of ecological source sites.Level 1 and 2 ecological sources(The ecological sources were categorized into level 1,level 2,and level 3 source from high to low importance.)are concentrated in the Emeishan basalt region of the upstream and the clastic and impure carbonate rock region of the downstream part of the BRB;level 3ecological sources are concentrated in the carbonate rock region of the midstream.Taking into account the outstanding ecological problems in the basin,and based on the characteristics of lithology and geohazard distribution,we propose the optimization scheme of“three axes,three zones and multiple points”for the ESP and the layout of specific measures of the BRB.The results can provide scientific references for maintaining ecological security maintenance in karst ecologically fragile areas.
基金supported by NIH/NIMH grant R01MH111619(to SQ),R21AG078700(to SQ)Institute of Mental Health Research(IMHR,Level 1 funding,to SQ and DF)institution startup fund from The University of Arizona(to SQ)。
文摘Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse function.We have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine morphogenesis.To investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing chow.We found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection neurons.These findings are further corroborated by increased synaptic activity and transient generation of immature silent synapses.Prolonged MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and connectivity.Our data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult brain.These findings may have implications for regenerative therapy in aging and neurodegeneration conditions.
文摘In the 9 December 2024 issue of Nature[1],a team of Google engineers reported breakthrough results using“Willow”,their lat-est quantum computing chip(Fig.1).By meeting a milestone“below threshold”reduction in the rate of errors that plague super-conducting circuit-based quantum computing systems(Fig.2),the work moves the field another step towards its promised super-charged applications,albeit likely still many years away.Areas expected to benefit from quantum computing include,among others,drug discovery,materials science,finance,cybersecurity,and machine learning.
基金the National Research Foundation(NRF)Singapore mid-sized center grant(NRF-MSG-2023-0002)FrontierCRP grant(NRF-F-CRP-2024-0006)+2 种基金A*STAR Singapore MTC RIE2025 project(M24W1NS005)IAF-PP project(M23M5a0069)Ministry of Education(MOE)Singapore Tier 2 project(MOE-T2EP50220-0014).
文摘The rise of large-scale artificial intelligence(AI)models,such as ChatGPT,Deep-Seek,and autonomous vehicle systems,has significantly advanced the boundaries of AI,enabling highly complex tasks in natural language processing,image recognition,and real-time decisionmaking.However,these models demand immense computational power and are often centralized,relying on cloud-based architectures with inherent limitations in latency,privacy,and energy efficiency.To address these challenges and bring AI closer to real-world applications,such as wearable health monitoring,robotics,and immersive virtual environments,innovative hardware solutions are urgently needed.This work introduces a near-sensor edge computing(NSEC)system,built on a bilayer AlN/Si waveguide platform,to provide real-time,energy-efficient AI capabilities at the edge.Leveraging the electro-optic properties of AlN microring resonators for photonic feature extraction,coupled with Si-based thermo-optic Mach-Zehnder interferometers for neural network computations,the system represents a transformative approach to AI hardware design.Demonstrated through multimodal gesture and gait analysis,the NSEC system achieves high classification accuracies of 96.77%for gestures and 98.31%for gaits,ultra-low latency(<10 ns),and minimal energy consumption(<0.34 pJ).This groundbreaking system bridges the gap between AI models and real-world applications,enabling efficient,privacy-preserving AI solutions for healthcare,robotics,and next-generation human-machine interfaces,marking a pivotal advancement in edge computing and AI deployment.
基金supported by the Beijing Natural Science Foundation(No.QY24166).
文摘In a pulsed plasma thruster,the voltage distribution between the electrodes is a key factor that influences the ionization process.However,few researchers have conducted in-depth studies of this phenomenon in the past.Reported here are measurements of the voltage distribution between the plates of a parallel-plate pulsed plasma thruster under different discharge voltages,based on which the variations in the total circuit inductance and resistance as well as those between the plates are calculated.The results show that the time-averaged voltage across the plates accounts for 28.7%-50.4%of the capacitor voltage.As the capacitor initial voltage increases from 1250 V to 2000 V,the voltage across the plates rises,but its proportion relative to the capacitor voltage decreases.For every 250 V increase in the capacitor initial voltage,the average voltage proportion across the plates decreases by approximately 2%-3%.Additionally,the voltage proportion decreases gradually from the end near the propellant outward.The voltage distribution ratio between the plates is correlated with the proportions of the resistance and inductance between the plates relative to the total circuit.
