Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.

Emerging insights into the function of very long chain fatty acids at cerebellar synapses

Very long chain-saturated and-polyunsaturated fatty acids(VLC-SFA and VLC-PUFA, respectively) are a functionally important class of fatty acids containing 28 carbons or more in their acyl chain. They are synthesized by the elongation of very long fatty acids-4(ELOVL4) enzyme, expressed mainly in the brain, retina, skin, testes, and meibomian gland, where these fatty acids are found(Agbaga et al., 2008). Further, these organs exhibit tissuespecific VLC-PUFA and VLC-SFA biosynthesis and incorporation into complex lipids for specific functions. In the brain, skin, and Meibomian glands, the ELOVL4 mainly makes VLC-SFA, which are incorporated into complex sphingolipids. In the retina, the ELOVL4 makes VLC-PUFA that are incorporated into phosphatidylcholine, that are critical for visual function, while in testes and sperm, the VLC-PUFA are incorporated into sphingolipids that are critical for fertility(Yeboah et al., 2021).

The complex role of protocadherin-19 in brain function:a focus on the oxytocin system

Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound,autism spectrum disorder,and other neuropsychiatric features including schizophrenia,anxiety,attentiondeficit/hyperactivity,and obsessive or aggressive behaviors.While seizures may become less frequent in adolescence,psychiatric comorbidities persist and often worsen with age(Dibbens et al.,2008;Kolc et al.,2020).

Neuropeptide cholecystokinin:a key neuromodulator for hippocampal functions

Spatial memory is crucial for survival within external surroundings and wild environments.The hippocampus,a critical hub for spatial learning and memory formation,has received extensive investigations on how neuromodulators shape its functions(Teixeira et al.,2018;Zhang et al.,2024).However,the landscape of neuromodulations in the hippocampal system remains poorly understood because most studies focus on classical monoamine neuromodulators,such as acetylcholine,serotonin,dopamine,and noradrenaline.The neuropeptides,comprising the most abundant neuromodulators in the central nervous system,play a pivotal role in neural information processing in the hippocampal system.Cholecystokinin(CCK),one of the most abundant neuropeptides,has been implicated in regulating various physiological and neurobiological statuses(Chen et al.,2019).CCK-A receptor(CCK-AR)and CCK-B receptors(CCK-BR)are two key receptors mediating the biological functions of CCK,both of which belong to class-A sevenfold transmembrane G protein-coupled receptors(Nishimura et al.,2015).CCK-AR preferentially reacts to sulfated CCK,whereas CCK-BR binds both CCK and gastrin with similar affinities(Ding et al.,2022).The expression patterns of CCK-AR and CCK-BR are distinct,implying that CCK has various functions in target regions.For instance,CCK-AR is widely expressed in the GI and brain subregions and is hence implicated in the control of digestive function and satiety regulation.Conversely,CCK-BR is abundantly and widely distributed in the central nervous system,which majorly regulates anxiety,learning,and memory(Ding et al.,2022).However,the roles of endogenous CCK and CCK receptors in regulating hippocampal function at electrophysiological and behavioral levels have received less attention.

Corrigendum: MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons

There is an error in the name of the cell line in the abstract of the published paper“MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons”published on pages 2698-2707,Issue 12,Volume 19 of Neural Regeneration Research(Sharma et al.,2024),because of oversight during final proof checking.The correct description should be“human-GABA receptor A-α1/β2/γ2L human embryonic kidney(HEK)recombinant cell line.”The authors apologize for any inconvenience this correction may cause for readers and editors of Neural Regeneration Research.

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.

Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise

Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

Characteristics and Functions of Cooperative Economic Organizations for Water-saving Irrigation in Agricultural Development in Arid Areas

Agricultural cooperative economic organization for water-saving irrigation in arid areas is a new form of economic organization in production,operation and management during the application process of water-saving irrigation technologies.Currently,there are few researches on this cooperative economic organization.In this study,connotations of cooperative economic organizations for water-saving irrigation are specifically defined,and the characteristics and functions of this cooperative economic organization are analyzed.Based on that,several suggestions are proposed on the continuous development of cooperative economic organizations for water-saving irrigation.

Economic polarized trends,function and expanded boundaries of the Yangtze Delta Region

In the era of economic globalization,the concept of Economic Polarized Area comes into being as an effective vehicle to agglomerate the economic elements and sustain the economic lifeline of the region. Based on the region's specific development mode and construction form the concept is working in such a way that it will contribute to guide the economic development of the country and will play an important role in competing with other regions or countries in the world. Due to the high speed development of the last 30 years,the Yangtze Delta Region starts to show the features of Economic Polarized Area. But,compared with other world-class Economic Polarized Areas,the economic strength and the ability of the Yangtze Delta Region to drive the country's economic development is still very low and the competitive power is still very limited. Expanding the boundaries of the Economic Polarized Area of the Yangtze Delta may extend the economic hinterland of the core area of the Yangtze Delta Region,will lighten the pressures from the limited resource and promote the rationalization of the industrial structure in the Yangtze Delta Region's core area. With regard to the reasonable boundaries of the Yangtze Delta Region,there are different opinions and controversial arguments in political and academic circles. Starting from the idea of increasing the competitive power and improving the economic strength of the Yangtze Delta Region,the paper firstly is discussing the requirements to become a world-class Economic Polarized Area. In a second step an analysis of functional complementation and economic collaboration between the cities of an "extended" Yangtze Delta Region has been carried out by in particular considering the feasibility of integrating these "newly included" cities. The final result of the study is,that the Region should be expanded from the number of 16 cities to 37 cities,and the appended cities should be divided up into two categories:Wenzhou,Jinhua,Yancheng,Huaian,Maanshan,Wuhu,Tongling,Chaohu,Hefei,Chuzhou,Xuancheng should be taken as Preferred Extending Area,and Suqian,Xuzhou,Lianyungang,Lishui,Quzhou,Chizhou,Anqing,Bengbu,Huangshan,Suzhou (Anhui Province) should be taken as Retained Qualification Area.

Three Types of Spatial Function Zoning in Key Ecological Function Areas Based on Ecological and Economic Coordinated Development: A Case Study of Tacheng Basin, China

Three types of spatial function zoning is an effective measure for regional environmental protection and orderly development.For ecological and economic coordinated development, spatial function zones should be divided scientifically to clear its direction of development and protection. Therefore, based on ecological constraints, a beneficial discussion would be about the key ecological function areas adopting the concept of ecological protection restriction and supporting socioeconomic development for spatial function zoning. In this paper, the researchers, taking Tacheng Basin, Xinjiang of China as an example, choose township as basic research unit and set up an evaluation index system from three aspects, namely, ecological protection suitability, agricultural production suitability, and urban development suitability, which are analyzed by using spatial analysis functions and exclusive matrix method. The results showed that: 1) This paper formed a set of multilevel evaluation index systems for three types of spatial function zoning of the key ecological function areas based on a novel perspective by scientifically dividing Tacheng Basin into ecological space, agricultural space, and urban space,which realized the integration and scientific orientation for spatial function at the township scale. 2) Under the guidance of three types of spatial pattern, the functional orientation and suggestions of development and protection was clearly defined for ecological protection zones,ecological economic zones, agricultural production zones, and urban development zones. 3) A new idea of space governance is provided to promote the coordinated and sustainable development between ecology and economy, which can break the traditional mode of thinking about regional economic development, and offers a scientific basis and reference for macro decision-making.

Study of Chinese Economic "Growth Drag" Caused by Land Resource in the Perspective of the Modified Two-Level CES Production Function

The purpose of the study is to measure the "growth drag" according to the characteristic of Chinese land resource.Romer model (2001) holds that every country is inevitably affected by the "growth drag" due to the limitation of land resource.So it's of profound strategic significance to measure the "growth drag" according to the character of Chinese land resource.Modified two-level CES production function was employed,and this paper modified the hypothesis of the model.The result indicates that the limitation of Chinese land resource casts shadow over the economic development of China,and the growth rate is 0.4618% lower than that without the limitation of land resource.Through implementing the land resource protection policy along with the technology improvement and the substitute effect of other factors to the land resource,China will keep a steady and balanced economic growth.

An Empirical Study on Rural Economic Growth in Hubei Province Based on New C-D Production Function

Human capital is becoming a major driving force of promoting economic growth and social development. Hubei Province as a large agricultural province is significantly affected by the human capital. The paper selects the correlation data about rural economic growth in Hubei Province as samples to analyze the contribution of physical capital and human capital to rural economic growth by the new C-D function and SPSS22. 0. The results show that the effect of the elasticity of human capital is greater than that of physical capital in rural economic development; the high quality rural human capital storage and the average years of schooling of rural labor force will increase the net income of rural household. Therefore,we should not only increase input of physical capital but also increase the input of human capital to raise the level of human capital in rural areas and promote sustainable development of rural economy.

The application of environmental economics in marine functional zoning and coastal city conceptual planning

There are a lot of functions of marine resources. The various and competing conflicts between different users and different sectors in the use of marine resources will cause the disorderly development of marine resources, and even destroy the marine ecosystem. Marine functional zoning is an effective tool to solve the conflicts. However, there are some shortcomings in the current understanding on marine functional zoning and its practice. In this paper, a case study on the resource-oriented marine functional zoning of Xiangshan Port is introduced. By the principles of resource-oriented and public participation, Xiangshan Port is divided into seven zones, and the main function of the whole port and seven zones are determined by the environmental economics analysis. A case study of Xiamen is also introduced for how to integrate marine functional zoning into a coastal city conceptual planning. Under the conservation principle, resources-oriented principle and so on, the advantages and disadvantages of natural ecosystem, social ecosystem and economic ecosystem are holistically analyzed, the urban orientation of Xiamen is determined as a regional international tourism city, and the whole city is divided into five function zones according to its leading industry -tourism. Resource-oriented marine functional zoning has a long-term guidance for sustainable use of marine resources and development strategy of a coastal city. And environmental economics analysis is an effective tool for resource-orientation.

Assessment of Stress Cognitive Control and Executive Function with Stress Control Rating Scale (ECOSTRESS) and Low Resolution Brain Electromagnetic Tomography (LORETA) (In Portuguese People in Situations of Unemployment and Economic Insufficiency)

This article reviews the constructs of stress, appraisal, coping, according to a transactional perspective, and executive function, and presents a stress control rating scale (ECOSTRESS), which design is founded in these constructs. This psychometric tool is useful in the assessment of cognitive control of stress, correlated with the function of dorsolateral prefrontal cortex. It has been validated for its use in the assessment of Portuguese people in situations of stress related to unemployment and economic insufficiency. Also, within the context of the cognitive control of stress, it is highlighted the usefulness of low resolution brain electromagnetic tomography (LORETA).

Spatial Function Regionalization Based on an Ecological-economic Analysis in Wuxi City, China

As a result of rapid urbanization in China, urban sprawl has increased rapidly, and land-use regulation and smart urban growth are equally important. Spatial function regionalization can provide the scientific groundwork for the regulation of land use and protection. This paper probes the system of evaluation indices and applies the methods of spatial analysis and classification clustering to the calculation of the ecologically significant value and economically significant value in each evaluation unit. After use of a classification matrix integrated by the two significant values, city space can be divided into four functional types, namely, feasible development area, moderate development area, moderate conservation area and prohibited exploiting area, and these are the basis for spatial development and control.

Economic Analysis on Monetization of Soil Functions

On the basis of making clear diversity characteristics of soil functions and multiple characteristics of income, this paper points out that the monetization of soil functions based functional maintenance and change decision process can be regarded as a game process of different utilization methods at the background of different functions. The balance of this game process will determine monetary value of soil functions. After understanding money and monetization concepts, it introduces that measurability and exchangeability of soil functions provide objective conditions for monetization of soil functions. Finally, it discusses that usefulness value of soil functions provide basis for monetization of soil functions.