In the last years, some studies have shown that behavior disorder seems in frontotemporal dementia is related to dysfunction in the fronto-subcortical circuitry. <strong>Objectives:</strong> We did a narra...In the last years, some studies have shown that behavior disorder seems in frontotemporal dementia is related to dysfunction in the fronto-subcortical circuitry. <strong>Objectives:</strong> We did a narrative literature review concerning fronto-subcortical circuitry and frontotemporal dementia (FTD). <strong>Methods:</strong> Manuscripts related to fronto-subcortical network and frontotemporal dementia were selected for further analysis. <strong>Results:</strong> From the executions of simple motor actions to the most complex behaviors like goal-direct behavior and social cognition, the fronto-subcortical circuitry involves an intrigued network of fibers that reaches to basal ganglia nuclei. Recently, researchers have shown five parallel fronto-subcortical circuits integrating and segregating information from the frontal cortex to basal ganglia. Understanding the relationship between the fronto-subcortical circuit dysfunctions and neurodegenerative diseases requires studying the functional anatomy and neurochemical basis involved.<strong> Conclusions:</strong> In this view, it is essential to review the functional anatomy of the fronto-subcortical network, and it’s correlated with clinical aspects to pursuing a better therapeutic approach.展开更多
Cerebral small vessel disease（CSVD） is a common etiology of vascular cognitive impairment with no dementia（V-CIND）. Studies have revealed that cerebral microbleeds（CMBs）, a feature of CSVD, contribute to cogniti...Cerebral small vessel disease（CSVD） is a common etiology of vascular cognitive impairment with no dementia（V-CIND）. Studies have revealed that cerebral microbleeds（CMBs）, a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients（29.3%） had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits（odds ratio = 4.4; 95% confidence interval： 1.602-12.081, P = 0.004） and 5 or more CMBs overall（odds ratio = 17.6, 95% confidence interval： 3.23-95.84, P = 0.001） had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs.展开更多
Fear memory,a predictive and protective mechanism in potentially hostile environments,elicits defensive behavioral responses that have evolved to help organisms avoid harm and ensure survival.However,excessive fear me...Fear memory,a predictive and protective mechanism in potentially hostile environments,elicits defensive behavioral responses that have evolved to help organisms avoid harm and ensure survival.However,excessive fear memories may contribute to the onset of various psychological disorders,such as panic disorder,phobias,and post-traumatic stress disorder(PTSD).展开更多
This paper introduces a switched hyperchaotic system that changes its behavior randomly from one subsystem to another via two switch functions, and its characteristics of symmetry, dissipation, equilibrium, bifurcatio...This paper introduces a switched hyperchaotic system that changes its behavior randomly from one subsystem to another via two switch functions, and its characteristics of symmetry, dissipation, equilibrium, bifurcation diagram, basic dynamics have been analyzed. The hardware implementation of the system is based on Field Programmable Gate Array (FPGA). It is shown that the experimental results are identical with numerical simulations, and the chaotic trajectories are much more complex.展开更多
The ability of the adult central nervous system to reorganize its circuits over time is the key to understand the functional improvement in subjects with spinal cord injury （SCI）. Adaptive changes within spared neur...The ability of the adult central nervous system to reorganize its circuits over time is the key to understand the functional improvement in subjects with spinal cord injury （SCI）. Adaptive changes within spared neuronal circuits may occur at cortical, brainstem, or spinal cord level, both above and below a spinal lesion （Bareyre et al., 2004）. At each level the reorganization is a very dynamic process, and its degree is highly variable, depending on several factors, including the age of the subject when SCI has occurred and the rehabilitative therapy. The use of electrophysiological techniques to assess these functional changes in neural networks is of great interest, because invasive methodologies as employed in preclinical models can obviously not be used in clinical studies.展开更多
Depression leads to a large social burden because of its substantial impairment and disability in everyday activities. The prevalence and considerable impact of this disorder call for a better understanding of its pat...Depression leads to a large social burden because of its substantial impairment and disability in everyday activities. The prevalence and considerable impact of this disorder call for a better understanding of its pathophysiology to improve the diagnosis, treatment and prevention. Though productive animal models and pathophysiological theories have been documented, it is still very far to uncover the complex array of symptoms caused by depression. Moreover, the neural circuitry mechanism underlying behavioral changes in some depression-like behavior animals is still limited. Changes in the neural circuitry of amygdala, dorsal raphe nucleus, ventral tegmental area, hippocampus, locus coeruleus and nucleus accumbens are related to depression. However, the interactions between individual neural circuitry of different brain areas, have not yet been fully elucidated. The purpose of the present review is to examine and summarize the current evidence for the pathophysiological mechanism of depression, with a focus on the neural circuitry, and emphasize the necessity and importance of integrating individual neural circuitry in different brain regions to understand depression.展开更多
Thalamocortical circuitry has a substantial impact on emotion and cognition.Previous studies have demonstrated alterations in thalamocortical functional connectivity(FC),characterized by region-dependent hypo-or hyper...Thalamocortical circuitry has a substantial impact on emotion and cognition.Previous studies have demonstrated alterations in thalamocortical functional connectivity(FC),characterized by region-dependent hypo-or hyper-connectivity,among individuals with major depressive disorder(MDD).However,the dynamical reconfiguration of the thalamocortical system over time and potential abnormalities in dynamic thalamocortical connectivity associated with MDD remain unclear.Hence,we analyzed dynamic FC(dFC)between ten thalamic subregions and seven cortical subnetworks from resting-state functional magnetic resonance images of 48 patients with MDD and 57 healthy controls(HCs)to investigate time-varying changes in thalamocortical FC in patients with MDD.Moreover,dynamic laterality analysis was conducted to examine the changes in functional lateralization of the thalamocortical system over time.Correlations between the dynamic measures of thalamocortical FC and clinical assessment were also calculated.We identified four dynamic states of thalamocortical circuitry wherein patients with MDD exhibited decreased fractional time and reduced transitions within a negative connectivity state that showed strong correlations with primary cortical networks,compared with the HCs.In addition,MDD patients also exhibited increased fluctuations in functional laterality in the thalamocortical system across the scan duration.The thalamo-subnetwork analysis unveiled abnormal dFC variability involving higher-order cortical networks in the MDD cohort.Significant correlations were found between increased dFC variability with dorsal attention and default mode networks and the severity of symptoms.Our study comprehensively investigated the pattern of alteration of the thalamocortical dFC in MDD patients.The heterogeneous alterations of dFC between the thalamus and both primary and higher-order cortical networks may help characterize the deficits of sensory and cognitive processing in MDD.展开更多
Mental health symptoms secondary to trauma exposure and substance use disorders(SUDs)co-occur frequently in both clinical and community samples.The possibility of a shared aetiology remains an important question in tr...Mental health symptoms secondary to trauma exposure and substance use disorders(SUDs)co-occur frequently in both clinical and community samples.The possibility of a shared aetiology remains an important question in translational neuroscience.Advancements in genetics,basic science,and neuroimaging have led to an improved understanding of the neural basis of these disorders,their frequent comorbidity and high rates of relapse remain a clinical challenge.This project aimed to conduct a review of the field’s current understanding regarding the neural circuitry underlying posttraumatic stress disorder and SUD.A comprehensive review was conducted of available published literature regarding the shared neurobiology of these disorders,and is summarized in detail,including evidence from both animal and clinical studies.Upon summarizing the relevant literature,this review puts forth a hypothesis related to their shared neurobiology within the context of fear processing and reward cues.It provides an overview of brain reward circuitry and its relation to the neurobiology,symptomology,and phenomenology of trauma and substance use.This review provides clinical insights and implications of the proposed theory,including the potential development of novel pharmacological and therapeutic treatments to address this shared neurobiology.Limitations and extensions of this theory are discussed to provide future directions and insights for this shared phenomena.展开更多
Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for pati...Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”展开更多
Sleep is an indispensable part of life−its deficiency has significant implications for overall health and wellbeing[1].In today’s fast-paced society,sleep loss from either stressful or non-stressful origins has becom...Sleep is an indispensable part of life−its deficiency has significant implications for overall health and wellbeing[1].In today’s fast-paced society,sleep loss from either stressful or non-stressful origins has become prevalent.Specifically,active sleep deprivation(ASD),resulting from extended use of smartphones and other recreational activities,has risen as a global health issue.Clinical research has underscored a strong correlation between chronic pain and inadequate sleep[2].The relationship between pain and sleep is reciprocal:pain disturbs sleep,while poor sleep quality,in turn,reduces pain tolerance and exacerbates spontaneous pain sensations[3].While these interplays are well-documented in cases of passive sleep deprivation(PSD)associated with external pressures or illnesses,understanding how and which regions of the brain collaborate to recalibrate the intricate neural circuitry governing pain perception during ASD remains a crucial yet unresolved frontier.展开更多
Osteoarthritis(OA),a debilitating joint disorder affecting millions worldwide,is characterized by persistent inflammation,oxidative stress,and irreversible cartilage breakdown,yet remains without diseasemodifying ther...Osteoarthritis(OA),a debilitating joint disorder affecting millions worldwide,is characterized by persistent inflammation,oxidative stress,and irreversible cartilage breakdown,yet remains without diseasemodifying therapies.Inspired by natural enzymatic cascades,we developed a bioinspired nanocomposite hydrogel,N,S-doped Mn-Nb(C-CeO),that mimics endogenous antioxidant pathways to reprogram the OA microenvironment.This system combines N,Sdoped Mn-Nb_(2)C MXene nanosheets with CeO_(2)nanozymes within a boronate ester-crosslinked hydrogel,forming an“immuno-redox circuitry”with four synergistic functions:(1)cascade reactive oxygen species(ROS)scavenging via superoxide dismutase-like Mn-Nb_(2)C and catalase-like CeO_(2),amplified by photothermal enhancement under near-infrared irradiation;(2)broad reactive nitrogen species clearance,removing peroxynitrite(ONOO^(-)),nitric oxide(NO),and nitroxyl(NO^(-))to mitigate inflammation;(3)immunomodulation through Mn^(2+)-activated cGAS-STING signaling,which promoted macrophage polarization toward the M2 phenotype,concomitantly reducing the levels of pro-inflammatory cytokines such as interleukin-1 beta(IL-1β)and tumor necrosis factor-alpha(TNF-α);(4)cartilage regeneration via pH/ROS-responsive simvastatin(SIM)release and nanocatalysis,upregulating SRY-box transcription factor 9(SOX9)and Col2a1 while inhibiting matrix metalloproteinase-13(MMP-13)and a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5).In a murine OA model,the system reduced synovitis by 60%,restored 80% of cartilage thickness,and suppressed osteophyte formation,outperforming singlecomponent treatments.This strategy pioneers a“self-healing cartilage”approach by integrating nanocatalysis with immunoengineering for transformative OA therapy.展开更多
文摘In the last years, some studies have shown that behavior disorder seems in frontotemporal dementia is related to dysfunction in the fronto-subcortical circuitry. <strong>Objectives:</strong> We did a narrative literature review concerning fronto-subcortical circuitry and frontotemporal dementia (FTD). <strong>Methods:</strong> Manuscripts related to fronto-subcortical network and frontotemporal dementia were selected for further analysis. <strong>Results:</strong> From the executions of simple motor actions to the most complex behaviors like goal-direct behavior and social cognition, the fronto-subcortical circuitry involves an intrigued network of fibers that reaches to basal ganglia nuclei. Recently, researchers have shown five parallel fronto-subcortical circuits integrating and segregating information from the frontal cortex to basal ganglia. Understanding the relationship between the fronto-subcortical circuit dysfunctions and neurodegenerative diseases requires studying the functional anatomy and neurochemical basis involved.<strong> Conclusions:</strong> In this view, it is essential to review the functional anatomy of the fronto-subcortical network, and it’s correlated with clinical aspects to pursuing a better therapeutic approach.
基金supported by the Medical Scientific Research Foundation of Guangdong Province,China(No.A2015160)
文摘Cerebral small vessel disease（CSVD） is a common etiology of vascular cognitive impairment with no dementia（V-CIND）. Studies have revealed that cerebral microbleeds（CMBs）, a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients（29.3%） had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits（odds ratio = 4.4; 95% confidence interval： 1.602-12.081, P = 0.004） and 5 or more CMBs overall（odds ratio = 17.6, 95% confidence interval： 3.23-95.84, P = 0.001） had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs.
基金supported by the National Natural Science Foundation of China(82104138)the Zhejiang Provincial Natural Science Foundation of China(LY24H310003).
文摘Fear memory,a predictive and protective mechanism in potentially hostile environments,elicits defensive behavioral responses that have evolved to help organisms avoid harm and ensure survival.However,excessive fear memories may contribute to the onset of various psychological disorders,such as panic disorder,phobias,and post-traumatic stress disorder(PTSD).
文摘This paper introduces a switched hyperchaotic system that changes its behavior randomly from one subsystem to another via two switch functions, and its characteristics of symmetry, dissipation, equilibrium, bifurcation diagram, basic dynamics have been analyzed. The hardware implementation of the system is based on Field Programmable Gate Array (FPGA). It is shown that the experimental results are identical with numerical simulations, and the chaotic trajectories are much more complex.
文摘The ability of the adult central nervous system to reorganize its circuits over time is the key to understand the functional improvement in subjects with spinal cord injury （SCI）. Adaptive changes within spared neuronal circuits may occur at cortical, brainstem, or spinal cord level, both above and below a spinal lesion （Bareyre et al., 2004）. At each level the reorganization is a very dynamic process, and its degree is highly variable, depending on several factors, including the age of the subject when SCI has occurred and the rehabilitative therapy. The use of electrophysiological techniques to assess these functional changes in neural networks is of great interest, because invasive methodologies as employed in preclinical models can obviously not be used in clinical studies.
文摘Depression leads to a large social burden because of its substantial impairment and disability in everyday activities. The prevalence and considerable impact of this disorder call for a better understanding of its pathophysiology to improve the diagnosis, treatment and prevention. Though productive animal models and pathophysiological theories have been documented, it is still very far to uncover the complex array of symptoms caused by depression. Moreover, the neural circuitry mechanism underlying behavioral changes in some depression-like behavior animals is still limited. Changes in the neural circuitry of amygdala, dorsal raphe nucleus, ventral tegmental area, hippocampus, locus coeruleus and nucleus accumbens are related to depression. However, the interactions between individual neural circuitry of different brain areas, have not yet been fully elucidated. The purpose of the present review is to examine and summarize the current evidence for the pathophysiological mechanism of depression, with a focus on the neural circuitry, and emphasize the necessity and importance of integrating individual neural circuitry in different brain regions to understand depression.
基金supported by the Science and Technology Innovation 2030-Major Projects(Nos.2021ZD0202000,2021ZD0200800,and 2021ZD0200701)the National Key Research and Development Program of China(No.2019YFA0706200)+1 种基金the National Natural Science Foundation of China(Nos.62227807,62202212,U21A20520,and U22A2033)the Science and Technology Program of Gansu Province(No.23YFGA0004),China.
文摘Thalamocortical circuitry has a substantial impact on emotion and cognition.Previous studies have demonstrated alterations in thalamocortical functional connectivity(FC),characterized by region-dependent hypo-or hyper-connectivity,among individuals with major depressive disorder(MDD).However,the dynamical reconfiguration of the thalamocortical system over time and potential abnormalities in dynamic thalamocortical connectivity associated with MDD remain unclear.Hence,we analyzed dynamic FC(dFC)between ten thalamic subregions and seven cortical subnetworks from resting-state functional magnetic resonance images of 48 patients with MDD and 57 healthy controls(HCs)to investigate time-varying changes in thalamocortical FC in patients with MDD.Moreover,dynamic laterality analysis was conducted to examine the changes in functional lateralization of the thalamocortical system over time.Correlations between the dynamic measures of thalamocortical FC and clinical assessment were also calculated.We identified four dynamic states of thalamocortical circuitry wherein patients with MDD exhibited decreased fractional time and reduced transitions within a negative connectivity state that showed strong correlations with primary cortical networks,compared with the HCs.In addition,MDD patients also exhibited increased fluctuations in functional laterality in the thalamocortical system across the scan duration.The thalamo-subnetwork analysis unveiled abnormal dFC variability involving higher-order cortical networks in the MDD cohort.Significant correlations were found between increased dFC variability with dorsal attention and default mode networks and the severity of symptoms.Our study comprehensively investigated the pattern of alteration of the thalamocortical dFC in MDD patients.The heterogeneous alterations of dFC between the thalamus and both primary and higher-order cortical networks may help characterize the deficits of sensory and cognitive processing in MDD.
文摘Mental health symptoms secondary to trauma exposure and substance use disorders(SUDs)co-occur frequently in both clinical and community samples.The possibility of a shared aetiology remains an important question in translational neuroscience.Advancements in genetics,basic science,and neuroimaging have led to an improved understanding of the neural basis of these disorders,their frequent comorbidity and high rates of relapse remain a clinical challenge.This project aimed to conduct a review of the field’s current understanding regarding the neural circuitry underlying posttraumatic stress disorder and SUD.A comprehensive review was conducted of available published literature regarding the shared neurobiology of these disorders,and is summarized in detail,including evidence from both animal and clinical studies.Upon summarizing the relevant literature,this review puts forth a hypothesis related to their shared neurobiology within the context of fear processing and reward cues.It provides an overview of brain reward circuitry and its relation to the neurobiology,symptomology,and phenomenology of trauma and substance use.This review provides clinical insights and implications of the proposed theory,including the potential development of novel pharmacological and therapeutic treatments to address this shared neurobiology.Limitations and extensions of this theory are discussed to provide future directions and insights for this shared phenomena.
文摘抑郁症发生发展与大脑奖赏和情绪调节环路功能失调密切相关,伏隔核(nucleus accumben,NAc)作为奖赏系统的核心枢纽,与腹侧被盖区(ventral tegmental area,VTA)、内侧前额叶皮质(medial prefrontal cortex,mPFC)、杏仁核(amygdala,AMY)、海马(hippocampus,HIP)及丘脑室旁核(paraventricular nucleus of the thalamus,PVT)等脑区构成的神经环路异常已被证实与抑郁症状存在显著关联。针刺通过多靶点起效的作用特点,符合抑郁症这一多病因、多系统失调的情感障碍特征。现基于NAc为中心的脑神经环路,系统梳理其在抑郁症发生发展中的功能变化及针刺干预的潜在机制,揭示针刺通过调节VTA-NAc多巴胺能传导、增强mPFC-NAc环路的神经递质平衡、双向调节AMY-NAc环路的情绪稳定、减轻HIP-NAc谷氨酸过度活跃状态及优化丘脑-NAc环路的兴奋性传递,实现对抑郁症的整体性改善。此外,该综述聚焦于环路层面的系统整合,突出了针刺抗抑郁的实用性及其机制研究进展,以期为临床治疗提供更可靠的理论支撑与实践指导。
基金supported by the National Natural Science Foundation of China,No.82174112(to PZ)Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine,No.22HHZYSS00015(to PZ)State-Sponsored Postdoctoral Researcher Program,No.GZC20231925(to LN)。
文摘Traumatic brain injury is a prevalent disorder of the central nervous system.In addition to primary brain parenchymal damage,the enduring biological consequences of traumatic brain injury pose long-term risks for patients with traumatic brain injury;however,the underlying pathogenesis remains unclear,and effective intervention methods are lacking.Intestinal dysfunction is a significant consequence of traumatic brain injury.Being the most densely innervated peripheral tissue in the body,the gut possesses multiple pathways for the establishment of a bidirectional“brain-gut axis”with the central nervous system.The gut harbors a vast microbial community,and alterations of the gut niche contribute to the progression of traumatic brain injury and its unfavorable prognosis through neuronal,hormonal,and immune pathways.A comprehensive understanding of microbiota-mediated peripheral neuroimmunomodulation mechanisms is needed to enhance treatment strategies for traumatic brain injury and its associated complications.We comprehensively reviewed alterations in the gut microecological environment following traumatic brain injury,with a specific focus on the complex biological processes of peripheral nerves,immunity,and microbes triggered by traumatic brain injury,encompassing autonomic dysfunction,neuroendocrine disturbances,peripheral immunosuppression,increased intestinal barrier permeability,compromised responses of sensory nerves to microorganisms,and potential effector nuclei in the central nervous system influenced by gut microbiota.Additionally,we reviewed the mechanisms underlying secondary biological injury and the dynamic pathological responses that occur following injury to enhance our current understanding of how peripheral pathways impact the outcome of patients with traumatic brain injury.This review aimed to propose a conceptual model for future risk assessment of central nervous system-related diseases while elucidating novel insights into the bidirectional effects of the“brain-gut-microbiota axis.”
基金supported by the National Natural Science Foundation of China(U21A20418).
文摘Sleep is an indispensable part of life−its deficiency has significant implications for overall health and wellbeing[1].In today’s fast-paced society,sleep loss from either stressful or non-stressful origins has become prevalent.Specifically,active sleep deprivation(ASD),resulting from extended use of smartphones and other recreational activities,has risen as a global health issue.Clinical research has underscored a strong correlation between chronic pain and inadequate sleep[2].The relationship between pain and sleep is reciprocal:pain disturbs sleep,while poor sleep quality,in turn,reduces pain tolerance and exacerbates spontaneous pain sensations[3].While these interplays are well-documented in cases of passive sleep deprivation(PSD)associated with external pressures or illnesses,understanding how and which regions of the brain collaborate to recalibrate the intricate neural circuitry governing pain perception during ASD remains a crucial yet unresolved frontier.
基金supported by the National Natural Science Foundation of China(Nos.82101647 and 82203446)Natural Science Fund of Zhejiang Province(Nos.LY24H250001,LQN25H060003,and LY23H060011)+2 种基金the Postdoctoral Fellowship Program of CPSF(No.188020-170257701/136)the Regional Innovation and Development Joint Fund of the National Natural Science Foundation of China(No.U22A20282)the Guangdong Basic and Applied Basic Research Foundation(No.2023A1515220225).
文摘Osteoarthritis(OA),a debilitating joint disorder affecting millions worldwide,is characterized by persistent inflammation,oxidative stress,and irreversible cartilage breakdown,yet remains without diseasemodifying therapies.Inspired by natural enzymatic cascades,we developed a bioinspired nanocomposite hydrogel,N,S-doped Mn-Nb(C-CeO),that mimics endogenous antioxidant pathways to reprogram the OA microenvironment.This system combines N,Sdoped Mn-Nb_(2)C MXene nanosheets with CeO_(2)nanozymes within a boronate ester-crosslinked hydrogel,forming an“immuno-redox circuitry”with four synergistic functions:(1)cascade reactive oxygen species(ROS)scavenging via superoxide dismutase-like Mn-Nb_(2)C and catalase-like CeO_(2),amplified by photothermal enhancement under near-infrared irradiation;(2)broad reactive nitrogen species clearance,removing peroxynitrite(ONOO^(-)),nitric oxide(NO),and nitroxyl(NO^(-))to mitigate inflammation;(3)immunomodulation through Mn^(2+)-activated cGAS-STING signaling,which promoted macrophage polarization toward the M2 phenotype,concomitantly reducing the levels of pro-inflammatory cytokines such as interleukin-1 beta(IL-1β)and tumor necrosis factor-alpha(TNF-α);(4)cartilage regeneration via pH/ROS-responsive simvastatin(SIM)release and nanocatalysis,upregulating SRY-box transcription factor 9(SOX9)and Col2a1 while inhibiting matrix metalloproteinase-13(MMP-13)and a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS5).In a murine OA model,the system reduced synovitis by 60%,restored 80% of cartilage thickness,and suppressed osteophyte formation,outperforming singlecomponent treatments.This strategy pioneers a“self-healing cartilage”approach by integrating nanocatalysis with immunoengineering for transformative OA therapy.
