Animal behavioral studies are often combined with research concerning cognitive abilities.Larger brains usually mean more complex neural networks and advanced cognitive functions.By measuring the brain size of differe...Animal behavioral studies are often combined with research concerning cognitive abilities.Larger brains usually mean more complex neural networks and advanced cognitive functions.By measuring the brain size of different individual animals,we can explore differences in behavioral complexity between populations or species.However,obtaining accurate measurements of brain size is challenging both in field and laboratory environments,especially for rare and endangered species.Therefore,there is an urgent need to develop reliable methods for performing cranial brain mass.This study tests which external structures of the avian head can most accurately predict brain size.We selected five bird species from four orders,categorized external head measures into three types of parameters(direct,calculated and composite measurements),and analyzed these in relation to brain mass.The results showed that while head size can partially explain brain mass,the parameters of head height x head width were the most accurate predictors of brain mass in birds(90.4%).In addition,the positive correlation between endocranial volume and brain mass once again confirmed that avian endocranial volume can,to a certain extent,serve as a valid proxy for brain mass.Our study demonstrates that in the future we can more conveniently perform non-invasive measurements to better understand the relationship between bird brain size and behavior,ecology,and evolution.展开更多
This paper reports a case of cerebral stem infarction with quadriplegia and complete dependence on daily life.The course of the disease lasted more than 7 months.Frenchay's improved articulation Disorder Assessmen...This paper reports a case of cerebral stem infarction with quadriplegia and complete dependence on daily life.The course of the disease lasted more than 7 months.Frenchay's improved articulation Disorder Assessment Form has been assessed as severe articulation disorder.The patient has significantly improved his speech function and quality of life after systematic head control training,respiratory function training,articulation motor training,and articulation training.In the course of treatment,emphasis was placed on head postural control training and respiratory function training,and emphasis was placed on the strength and coordination training of articulatory organs,and the results were remarkable.After the patient was discharged from the hospital,the follow-up of basic daily life communication was not limited.展开更多
Car-to-pedestrian collision(CPC)accidents occur frequently,and pedestrians often suffer serious head/brain injuries.One major cause is the primary impact with the windshield.Here,we use an umerical sim ulation method ...Car-to-pedestrian collision(CPC)accidents occur frequently,and pedestrians often suffer serious head/brain injuries.One major cause is the primary impact with the windshield.Here,we use an umerical sim ulation method to study the influence of the windshield in-clination angle of a passenger car on pedestrian head/brain injury due to CPC accidents.The range of the windshield inclination angle was set at 24°-50°,with an interval of 2°.The results show that the windshield angle significantly affects the pedestrian kine-matics and exerts different effects on the head injury when evaluating with various head injury criteria.Regarding the head peak linear/rotational acceleration and acceleration-based head injury criterion(HIC)/rotational injury criterion(RIC),the predictions at the secondary impact stage have no clear relationship with the windshield angle(R^(2)=0.04,0.07,0.03 and 0.26,respectively)and their distributions are scattered.In the primary impact,the peak linear acceleration and HIC show a weak trend of first decreasing and then increasing with the increasing of the windshield angle,and the rotational acceleration and RIC tend to remain relatively con-stant.Regarding the cum ulative strain dama ge measure(CSDM)criterion,the predictions at the primary impact are slightly lower than those at the secondary impact,and the trend of first decreasing and then increasing with the increase in the windshield angle is observed at both impact stages.When the windshield inclination angle is approximately 32°-40°,the head injury severity in both impact phases is generally lower than that predicted at other windshield angles.展开更多
OBJECTIVE: To analyze part of the mechanism of electroacupuncture on Sishencong(EX-HN1) for strokerelated sleep disorders(SSD) and post-stroke cognitive impairment(PSCI). METHODS: Using a randomized controlled trial(R...OBJECTIVE: To analyze part of the mechanism of electroacupuncture on Sishencong(EX-HN1) for strokerelated sleep disorders(SSD) and post-stroke cognitive impairment(PSCI). METHODS: Using a randomized controlled trial(RCT) design, 72 patients were assigned to the electroacupuncture(EA) group or the sham acupuncture(SA) group. A healthy control(HC) group was also included. Both groups were given routine rehabilitation treatment. Then, patients in the EA group were given additional electroacupuncture at Sishencong(EX_HN1). Meanwhile, patients in the SA group were given a flat-head needle sham/placebo treatment placed at the bilateral Jianyu (LI15) and Binao(LI14) line midpoints and the Jianyu(LI15) and Jianzhen(SI9) line midpoints. Before and after treatment, scales were collected and analyzed. In the second phase of the study, some subjects from the EA group were selected for functional magnetic resonance imaging(f MRI) data acquisition and comparative analysis with the HC group using a non-RCT design. RESULTS: The EA group performed better than the SA group on the Pittsburgh sleep quality index(PSQI), Montreal cognitive assessment basic(Mo CA_B), selfrating anxiety scale(SAS), and self-rating depression scale(SDS). Analysis of the f MRI showed that lowfrequency(2 Hz) electroacupuncture stimulation at Sishencong(EX_HN1) can restrain frontal sup medial right(SFGmed.R), precuneus right(PCUN.R), and posterior cingulate cortex right(PCC.R) and enhance angular left(ANG.L), parietal inf left(IPL.L) and occipital mid left(MOG.L). The functional connectivity(FC) of SFGmed.R was positively correlated with PSQI. Electroacupuncture stimulation at Sishencong(EX_HN1) can reduce the side efficiency of the whole brain connection with the Thalamus.L, Hippocampus.L, and Occipital.Mid.L. CONCLUSIONS: Low frequency(2 Hz) electroacupuncture stimulation at Sishencong(EX_HN1) can simultaneously improve sleep quality, negative emotions, and cognitive functions, the first two of which may be related to SFGmed.R restraint. Electroacupuncture can make some brain areas approach the physiological bias state, which is characterized by dominant hemispheric enhancement and non-dominant hemispheric weakening. The reduced whole brain connection side efficiency with some key nodes of the brain net may relate to sleep quality improvements in SSD patients.展开更多
Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact...Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact underlying mechanism remains largely unknown.Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH.In this study,a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery.Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage.Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum,temporal lobe/cortex,and hippocampal regions during the early stages of PTH.Additionally,variations in brain functional activities and connectivity were further detected in the early stage of PTH,particularly in the cerebellum and temporal cortex,suggesting that these regions play central roles in the mechanism underlying PTH.Moreover,our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH.Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex,with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.展开更多
The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting...The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.展开更多
Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela ...Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.展开更多
Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells ...Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological recovery.However,the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear.In this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 expression.However,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial activation.In agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice.Notably,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head injury.In conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry,thereby promoting induced neural stem cell–mediated improvement of neuronal injury,cerebral edema,and neurological disorders following closed head injury.展开更多
Terahertz biotechnology has been increasingly applied in various biomedical fields and has especially shown great potential for application in brain sciences.In this article,we review the development of terahertz biot...Terahertz biotechnology has been increasingly applied in various biomedical fields and has especially shown great potential for application in brain sciences.In this article,we review the development of terahertz biotechnology and its applications in the field of neuropsychiatry.Available evidence indicates promising prospects for the use of terahertz spectroscopy and terahertz imaging techniques in the diagnosis of amyloid disease,cerebrovascular disease,glioma,psychiatric disease,traumatic brain injury,and myelin deficit.In vitro and animal experiments have also demonstrated the potential therapeutic value of terahertz technology in some neuropsychiatric diseases.Although the precise underlying mechanism of the interactions between terahertz electromagnetic waves and the biosystem is not yet fully understood,the research progress in this field shows great potential for biomedical noninvasive diagnostic and therapeutic applications.However,the biosafety of terahertz radiation requires further exploration regarding its two-sided efficacy in practical applications.This review demonstrates that terahertz biotechnology has the potential to be a promising method in the field of neuropsychiatry based on its unique advantages.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
The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even...The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.展开更多
Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In ...Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.展开更多
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-0...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.展开更多
Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indic...Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indicate that bone and brain can influence each other’s homeostasis via multiple pathways,yet there is a dearth of systematic reviews in this area.This review comprehensively examines interactions across three key areas:the influence of bone-derived factors on brain function,the effects of brain-related diseases or injuries(BRDI)on bone health,and the concept of skeletal interoception.Additionally,the review discusses innovative approaches in biomaterial design inspired by bone-brain interaction mechanisms,aiming to facilitate bonebrain interactions through materiobiological effects to aid in the treatment of neurodegenerative and bone-related diseases.Notably,the integration of artificial intelligence(AI)in biomaterial design is highlighted,showcasing AI’s role in expediting the formulation of effective and targeted treatment strategies.In conclusion,this review offers vital insights into the mechanisms of bone-brain interaction and suggests advanced approaches to harness these interactions in clinical practice.These insights offer promising avenues for preventing and treating complex diseases impacting the skeleton and brain,underscoring the potential of interdisciplinary approaches in enhancing human health.展开更多
The current artificial bone is unable to accurately replicate the inhomogeneity and anisotropy of human cancellous bone.To address this issue,we proposed a personalized approach based on clinical CT images to design m...The current artificial bone is unable to accurately replicate the inhomogeneity and anisotropy of human cancellous bone.To address this issue,we proposed a personalized approach based on clinical CT images to design mechanical equivalent porous structures for artificial femoral heads.Firstly,supported by Micro and clinical CT scans of 21 bone specimens,the anisotropic mechanical parameters of human cancellous bone in the femoral head were characterized using clinical CT values(Hounsfield unit).After that,the equivalent porous structure of cancellous bone was designed based on the gyroid surface,the influence of its degree of anisotropy and volume fraction on the macroscopic mechanical parameters was investigated by finite element analysis.Furthermore,a mapping relationship between CT values and the porous structure was established by jointly solving the mechanical parameters of the porous structure and human cancellous bone,allowing the design of personalized gradient porous structures based on clinical CT images.Finally,to verify the mechanical equivalence,implant press-in tests were conducted on 3D-printed artificial femoral heads and human femoral heads,the influence of the porous structure’s cell size in bone-implant interaction problems was also explored.Results showed that the minimum deviations of press-in stiffness(<15%)and peak load(<5%)both occurred when the cell size was 20%to 30%of the implant diameter.In conclusion,the designed porous structure can replicate the human cancellous bone-implant interaction at a high level,indicating its effectiveness in optimizing the mechanical performance of 3D-printed artificial femoral head.展开更多
Dear Editor,Local recurrence and cervical lymph node metastases are major causes of mortality in patients with head and neck squamous cell carcinoma(HNSCC).To date,none of the proposed strategies for predicting outcom...Dear Editor,Local recurrence and cervical lymph node metastases are major causes of mortality in patients with head and neck squamous cell carcinoma(HNSCC).To date,none of the proposed strategies for predicting outcomes in this disease have proven fully effective,and a comprehensive physical examination remains the primary method for early detection and monitoring of HNSCC.展开更多
The integration of the digital economy with the traditional sales industry has prompted the robust growth of e-commerce.Live-streaming e-commerce,as a novel business model,has gained immense popularity.However,is⁃sues...The integration of the digital economy with the traditional sales industry has prompted the robust growth of e-commerce.Live-streaming e-commerce,as a novel business model,has gained immense popularity.However,is⁃sues of regulatory loopholes and inefficacy continue to surface.In live-streaming e-commerce,the head anchor,as host of the live-streaming rooms,wields significant influence in determining the goods to be showcased and marketed.Such influence expands risks such as infringement of intellectual property rights.Yet the uncertainty in law concerning the identity of head anchors results in a lack of accountability.Current norms are inadequate in constraining the group of head anchors.Drawing on the principles of risk control,the alignment between benefit and risk,and the theory of so⁃cial cost control,this paper argues that it is both justifiable and feasible to impose a duty to exercise reasonable care on head anchors.To effectively enshrine this duty in law,it is of great importance to redefine the mechanism of identifying the duty of care of head anchors in live-streaming e-commerce.In particular,the contents of the duty of care under⁃taken by head anchors and the consequences of breaching such a duty of care should be clarified.展开更多
A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati...A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.展开更多
基金supported by the National Key R&D Program of China(2023YFF1304600)。
文摘Animal behavioral studies are often combined with research concerning cognitive abilities.Larger brains usually mean more complex neural networks and advanced cognitive functions.By measuring the brain size of different individual animals,we can explore differences in behavioral complexity between populations or species.However,obtaining accurate measurements of brain size is challenging both in field and laboratory environments,especially for rare and endangered species.Therefore,there is an urgent need to develop reliable methods for performing cranial brain mass.This study tests which external structures of the avian head can most accurately predict brain size.We selected five bird species from four orders,categorized external head measures into three types of parameters(direct,calculated and composite measurements),and analyzed these in relation to brain mass.The results showed that while head size can partially explain brain mass,the parameters of head height x head width were the most accurate predictors of brain mass in birds(90.4%).In addition,the positive correlation between endocranial volume and brain mass once again confirmed that avian endocranial volume can,to a certain extent,serve as a valid proxy for brain mass.Our study demonstrates that in the future we can more conveniently perform non-invasive measurements to better understand the relationship between bird brain size and behavior,ecology,and evolution.
基金Teaching and Research Project of Anhui Urban Management Vocational College(Project No.:2024kfkc001)。
文摘This paper reports a case of cerebral stem infarction with quadriplegia and complete dependence on daily life.The course of the disease lasted more than 7 months.Frenchay's improved articulation Disorder Assessment Form has been assessed as severe articulation disorder.The patient has significantly improved his speech function and quality of life after systematic head control training,respiratory function training,articulation motor training,and articulation training.In the course of treatment,emphasis was placed on head postural control training and respiratory function training,and emphasis was placed on the strength and coordination training of articulatory organs,and the results were remarkable.After the patient was discharged from the hospital,the follow-up of basic daily life communication was not limited.
基金supported by the National Natural Science Funds for Distinguished Young Sc holar(Gr ant No.52325211)National Natural Science Foundation of China(Grants No.52172399 and 52372348)+1 种基金Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Pro vince,Natural Science Foundation of Changsha(Grant No.KQ2208235)Chongqing Ph.D.‘Through Train’Scientific Research Project(Grant No.s1202100000528).
文摘Car-to-pedestrian collision(CPC)accidents occur frequently,and pedestrians often suffer serious head/brain injuries.One major cause is the primary impact with the windshield.Here,we use an umerical sim ulation method to study the influence of the windshield in-clination angle of a passenger car on pedestrian head/brain injury due to CPC accidents.The range of the windshield inclination angle was set at 24°-50°,with an interval of 2°.The results show that the windshield angle significantly affects the pedestrian kine-matics and exerts different effects on the head injury when evaluating with various head injury criteria.Regarding the head peak linear/rotational acceleration and acceleration-based head injury criterion(HIC)/rotational injury criterion(RIC),the predictions at the secondary impact stage have no clear relationship with the windshield angle(R^(2)=0.04,0.07,0.03 and 0.26,respectively)and their distributions are scattered.In the primary impact,the peak linear acceleration and HIC show a weak trend of first decreasing and then increasing with the increasing of the windshield angle,and the rotational acceleration and RIC tend to remain relatively con-stant.Regarding the cum ulative strain dama ge measure(CSDM)criterion,the predictions at the primary impact are slightly lower than those at the secondary impact,and the trend of first decreasing and then increasing with the increase in the windshield angle is observed at both impact stages.When the windshield inclination angle is approximately 32°-40°,the head injury severity in both impact phases is generally lower than that predicted at other windshield angles.
基金the National Natural Science Foundation of China Project:the Study of Central Mechanism of Electroacupuncture on Sishencong (EX-HN1) Improving Sleep Architecture and Neurocognitive Function Using Electroencephalogram-Functional Magnetic Resonance Imaging (No. 81774426)Major Scientific Research Project of Wuxi Health Commission:Clinical Study of Intelligent Hand Rehabilitation Training System for Nerve Function Reconstruction of Patients with Hand Dysfunction after Cerebral Infarction (No. Z202121)。
文摘OBJECTIVE: To analyze part of the mechanism of electroacupuncture on Sishencong(EX-HN1) for strokerelated sleep disorders(SSD) and post-stroke cognitive impairment(PSCI). METHODS: Using a randomized controlled trial(RCT) design, 72 patients were assigned to the electroacupuncture(EA) group or the sham acupuncture(SA) group. A healthy control(HC) group was also included. Both groups were given routine rehabilitation treatment. Then, patients in the EA group were given additional electroacupuncture at Sishencong(EX_HN1). Meanwhile, patients in the SA group were given a flat-head needle sham/placebo treatment placed at the bilateral Jianyu (LI15) and Binao(LI14) line midpoints and the Jianyu(LI15) and Jianzhen(SI9) line midpoints. Before and after treatment, scales were collected and analyzed. In the second phase of the study, some subjects from the EA group were selected for functional magnetic resonance imaging(f MRI) data acquisition and comparative analysis with the HC group using a non-RCT design. RESULTS: The EA group performed better than the SA group on the Pittsburgh sleep quality index(PSQI), Montreal cognitive assessment basic(Mo CA_B), selfrating anxiety scale(SAS), and self-rating depression scale(SDS). Analysis of the f MRI showed that lowfrequency(2 Hz) electroacupuncture stimulation at Sishencong(EX_HN1) can restrain frontal sup medial right(SFGmed.R), precuneus right(PCUN.R), and posterior cingulate cortex right(PCC.R) and enhance angular left(ANG.L), parietal inf left(IPL.L) and occipital mid left(MOG.L). The functional connectivity(FC) of SFGmed.R was positively correlated with PSQI. Electroacupuncture stimulation at Sishencong(EX_HN1) can reduce the side efficiency of the whole brain connection with the Thalamus.L, Hippocampus.L, and Occipital.Mid.L. CONCLUSIONS: Low frequency(2 Hz) electroacupuncture stimulation at Sishencong(EX_HN1) can simultaneously improve sleep quality, negative emotions, and cognitive functions, the first two of which may be related to SFGmed.R restraint. Electroacupuncture can make some brain areas approach the physiological bias state, which is characterized by dominant hemispheric enhancement and non-dominant hemispheric weakening. The reduced whole brain connection side efficiency with some key nodes of the brain net may relate to sleep quality improvements in SSD patients.
基金supported by the Natural Science Foundation of Guangdong Province,China(2021A1515010897)Discipline Construction Fund of Central People’s Hospital of Zhanjiang(2020A01,2020A02)+1 种基金National Natural Science Foundation of China(31970973,21921004,32271148)Biosecurity Research Project(23SWAQ24)。
文摘Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact underlying mechanism remains largely unknown.Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH.In this study,a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery.Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage.Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum,temporal lobe/cortex,and hippocampal regions during the early stages of PTH.Additionally,variations in brain functional activities and connectivity were further detected in the early stage of PTH,particularly in the cerebellum and temporal cortex,suggesting that these regions play central roles in the mechanism underlying PTH.Moreover,our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH.Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex,with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.
基金supported by the grants from the Spanish Ministry of Economy and Competitiveness(SAF2017-85602-R)the Spanish Ministry of Science and Innovation(PID2020-119638RB-I00 to EGR)FPU-program(FPU17/02616 to JCG)。
文摘The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.
文摘Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.
基金supported by the National Natural Science Foundation of China,Nos.82271397(to MG),82001293(to MG),82171355(to RX),81971295(to RX),and 81671189(to RX)。
文摘Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological recovery.However,the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear.In this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 expression.However,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial activation.In agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice.Notably,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head injury.In conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry,thereby promoting induced neural stem cell–mediated improvement of neuronal injury,cerebral edema,and neurological disorders following closed head injury.
基金supported by grants from the National Key R&D Program of China,No.2017YFC0909200(to DC)the National Natural Science Foundation of China,No.62075225(to HZ)+1 种基金Zhejiang Provincial Medical Health Science and Technology Project,No.2023XY053(to ZP)Zhejiang Provincial Traditional Chinese Medical Science and Technology Project,No.2023ZL703(to ZP).
文摘Terahertz biotechnology has been increasingly applied in various biomedical fields and has especially shown great potential for application in brain sciences.In this article,we review the development of terahertz biotechnology and its applications in the field of neuropsychiatry.Available evidence indicates promising prospects for the use of terahertz spectroscopy and terahertz imaging techniques in the diagnosis of amyloid disease,cerebrovascular disease,glioma,psychiatric disease,traumatic brain injury,and myelin deficit.In vitro and animal experiments have also demonstrated the potential therapeutic value of terahertz technology in some neuropsychiatric diseases.Although the precise underlying mechanism of the interactions between terahertz electromagnetic waves and the biosystem is not yet fully understood,the research progress in this field shows great potential for biomedical noninvasive diagnostic and therapeutic applications.However,the biosafety of terahertz radiation requires further exploration regarding its two-sided efficacy in practical applications.This review demonstrates that terahertz biotechnology has the potential to be a promising method in the field of neuropsychiatry based on its unique advantages.
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,No.81921006(to GHL)。
文摘The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.
基金supported by the Fundamental Research Program of Shanxi Province of China,No.20210302124277the Science Foundation of Shanxi Bethune Hospital,No.2021YJ13(both to JW)。
文摘Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.
基金supported by the National Natural Science Foundation of China,Nos.82204360(to HM)and 82270411(to GW)National Science and Technology Innovation 2030 Major Program,No.2021ZD0200900(to YL)。
文摘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.
基金financially supported by the Basic Science Center Program(T2288102)the Key Program of the National Natural Science Foundation of China(32230059)+3 种基金the Foundation of Frontiers Science Center for Materiobiology and Dynamic Chemistry(JKVD1211002)the Project supported by the Young Scientists Fund of the National Natural Science Foundation of China(32401128)Postdoctoral Fellowship Program of CPSF(GZC20230793)Shanghai Post-doctoral Excellence Program(2023251).
文摘Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indicate that bone and brain can influence each other’s homeostasis via multiple pathways,yet there is a dearth of systematic reviews in this area.This review comprehensively examines interactions across three key areas:the influence of bone-derived factors on brain function,the effects of brain-related diseases or injuries(BRDI)on bone health,and the concept of skeletal interoception.Additionally,the review discusses innovative approaches in biomaterial design inspired by bone-brain interaction mechanisms,aiming to facilitate bonebrain interactions through materiobiological effects to aid in the treatment of neurodegenerative and bone-related diseases.Notably,the integration of artificial intelligence(AI)in biomaterial design is highlighted,showcasing AI’s role in expediting the formulation of effective and targeted treatment strategies.In conclusion,this review offers vital insights into the mechanisms of bone-brain interaction and suggests advanced approaches to harness these interactions in clinical practice.These insights offer promising avenues for preventing and treating complex diseases impacting the skeleton and brain,underscoring the potential of interdisciplinary approaches in enhancing human health.
基金supported by the National Key R&D Program of China(Grant No.2021YFC2501700).
文摘The current artificial bone is unable to accurately replicate the inhomogeneity and anisotropy of human cancellous bone.To address this issue,we proposed a personalized approach based on clinical CT images to design mechanical equivalent porous structures for artificial femoral heads.Firstly,supported by Micro and clinical CT scans of 21 bone specimens,the anisotropic mechanical parameters of human cancellous bone in the femoral head were characterized using clinical CT values(Hounsfield unit).After that,the equivalent porous structure of cancellous bone was designed based on the gyroid surface,the influence of its degree of anisotropy and volume fraction on the macroscopic mechanical parameters was investigated by finite element analysis.Furthermore,a mapping relationship between CT values and the porous structure was established by jointly solving the mechanical parameters of the porous structure and human cancellous bone,allowing the design of personalized gradient porous structures based on clinical CT images.Finally,to verify the mechanical equivalence,implant press-in tests were conducted on 3D-printed artificial femoral heads and human femoral heads,the influence of the porous structure’s cell size in bone-implant interaction problems was also explored.Results showed that the minimum deviations of press-in stiffness(<15%)and peak load(<5%)both occurred when the cell size was 20%to 30%of the implant diameter.In conclusion,the designed porous structure can replicate the human cancellous bone-implant interaction at a high level,indicating its effectiveness in optimizing the mechanical performance of 3D-printed artificial femoral head.
文摘Dear Editor,Local recurrence and cervical lymph node metastases are major causes of mortality in patients with head and neck squamous cell carcinoma(HNSCC).To date,none of the proposed strategies for predicting outcomes in this disease have proven fully effective,and a comprehensive physical examination remains the primary method for early detection and monitoring of HNSCC.
文摘The integration of the digital economy with the traditional sales industry has prompted the robust growth of e-commerce.Live-streaming e-commerce,as a novel business model,has gained immense popularity.However,is⁃sues of regulatory loopholes and inefficacy continue to surface.In live-streaming e-commerce,the head anchor,as host of the live-streaming rooms,wields significant influence in determining the goods to be showcased and marketed.Such influence expands risks such as infringement of intellectual property rights.Yet the uncertainty in law concerning the identity of head anchors results in a lack of accountability.Current norms are inadequate in constraining the group of head anchors.Drawing on the principles of risk control,the alignment between benefit and risk,and the theory of so⁃cial cost control,this paper argues that it is both justifiable and feasible to impose a duty to exercise reasonable care on head anchors.To effectively enshrine this duty in law,it is of great importance to redefine the mechanism of identifying the duty of care of head anchors in live-streaming e-commerce.In particular,the contents of the duty of care under⁃taken by head anchors and the consequences of breaching such a duty of care should be clarified.
基金supported by the National Natural Science Foundation of China,No.82001155(to LL)the Natural Science Foundation of Zhejiang Province,No.LY23H090004(to LL)+5 种基金the Natural Science Foundation of Ningbo,No.2023J068(to LL)the Fundamental Research Funds for the Provincial Universities of Zhejiang Province,No.SJLY2023008(to LL)the College Students'Scientific and Technological Innovation Project(Xin Miao Talent Plan)of Zhejiang Province,No.2022R405A045(to CC)the Student ResearchInnovation Program(SRIP)of Ningbo University,Nos.20235RIP1919(to CZ),2023SRIP1938(to YZ)the K.C.Wong Magna Fund in Ningbo University。
文摘A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.
