Rhododendron micranthum Turcz.is a shrub esteemed for its ornamental and medicinal attributes within the Changbai Mountain range of China.We selected 3-year saplings and subjected them to four distinct light condi-tio...Rhododendron micranthum Turcz.is a shrub esteemed for its ornamental and medicinal attributes within the Changbai Mountain range of China.We selected 3-year saplings and subjected them to four distinct light condi-tions:full light(CK),70%light(L1),50%light(L2),and 30%light(L3)to investigate variations in morphology,photosynthetic responses,stomatal ultrastructure as well as the mechanisms through which these saplings adapt to differing lighting environments.The results indicate that L2 leaves exhibit significantly greater length,width,and petiole development compared to other treatments across varying intensities.Over time,chlorophyll content and PSII levels in L2-treated saplings surpass those observed in other treatments;Proline(PRO),malondialdehyde(MDA),and soluble protein(SP)contents are markedly lower under L2 treatment.Catalase(CAT)and superoxide dismutase(SOD)demonstrate significant correlations across various light con-ditions but respond differently among treatments,indicat-ing distinct species sensitivities to light intensity while both contribute to environmental stress resistance mechanisms.Findings reveal that R.micranthum saplings at 50%light intensity benefit from enhanced protection via antioxidant enzymes,and shading reduces osmotic adjustment sub-stances yet increases chlorophyll content.Stomatal length/width along with conductance rates and net photosynthesis rates for L2 exceed those of CK,suggesting an improved photosynthetic structure conducive to efficient photosynthe-sis under this condition.Thus,moderate shading represents optimal growth at 50%illumination,a critical factor promot-ing sapling development.This research elucidates the ideal environment for R.micranthum adaptation to varying light conditions supporting future conservation initiatives.展开更多
Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewa...Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewable,and clinical demand is increasingly difficult to meet,leading to a proliferation of counterfeit products.During prolonged geological burial,static pressure from the surrounding strata severely compromises the microstructural integrity of osteons in Os Draconis,but Os Draconis still largely retains the structural features of mammalian bone.Methods:Using verified authentic Os Draconis samples over 10,000 years old as a baseline,this study summarizes the ultrastructural characteristics of genuine Os Draconis.Employing electron probe microanalysis and optical polarized light microscopy,we examined 28 batches of authentic Os Draconis and 31 batches of counterfeits to identify their ultrastructural differences.Key points for ultrastructural identification of Os Draconis were compiled,and a new identification approach was proposed based on these differences.Results:Authentic Os Draconis exhibited distinct ultrastructural markers:irregularly shaped osteons with traversing fissures,deformed/displaced Haversian canals,and secondary mineral infill(predominantly calcium carbonate).Counterfeits showed regular osteon arrangements,absent traversal fissures,and homogeneous hydroxyapatite composition.Lab-simulated samples lacked structural degradation features.EPMA confirmed calcium carbonate infill in fossilized Haversian canals,while elemental profiles differentiated lacunae types(void vs.mineral-packed).Conclusion:The study established ultrastructural criteria for authentic Os Draconis identification:osteon deformation,geological fissures penetrating bone units,and heterogenous mineral deposition.These features,unattainable in counterfeits or modern processed bones,provide a cost-effective,accurate identification method.This approach bridges gaps in TCM material standardization and supports quality control for clinical applications.展开更多
The giant triton snail Charonia tritonis is a marine large carnivorous gastropoda inhabiting in the Indo-Pacific Ocean.Their splendid and highly organized Charonia tritonis shells are attractive;however few studies ha...The giant triton snail Charonia tritonis is a marine large carnivorous gastropoda inhabiting in the Indo-Pacific Ocean.Their splendid and highly organized Charonia tritonis shells are attractive;however few studies have been conducted on shell ultra-structure and pigmentation.The arrangements of crossed-lamellar structures were distinctive for the giant triton snail shell,showing three layers of mineral structures in the cross-section.The 1st-order and 2nd-order lamellae of the shell were around 10-20μm and the crystals in outer layers intersected at right angles in this species.They were identified as aragonite crystals by Raman scattering,and granular organic matrix were attached to the aragonite mineral phase closely.Furthermore,the dominant Raman spectra from polyene pigments in the shell were characterized at wavenumbers of 1123 cm^(-1)and 1504 cm^(-1),assigned to stretching vibrations of carbon-carbon single(C-C)and double(C=C)bonds,and the polyene chain was confirmed with 11-12 C-C bonds and 12-13 conju-gated C=C bonds.The research will lay a foundation for exploring the relationship between the calcareous shell and the formation of shell color in the giant triton snail.展开更多
This study aimed to investigate aquaporin 4 expression and the ultrastructure of the blood-brain barrier at 2-72 hours following cerebral contusion injury, and correlate these changes to the formation of brain edema. ...This study aimed to investigate aquaporin 4 expression and the ultrastructure of the blood-brain barrier at 2-72 hours following cerebral contusion injury, and correlate these changes to the formation of brain edema. Results revealed that at 2 hours after cerebral contusion and laceration injury, aquaporin 4 expression significantly increased, brain water content and blood-brain barrier permeability increased, and the number of pinocytotic vesicles in cerebral microvascular endothelia cells increased. In addition, the mitochondrial accumulation was observed. As contusion and laceration injury became aggravated, aquaporin 4 expression continued to increase, brain water content and blood-brain barrier permeability gradually increased, brain capillary endothelial cells and astrocytes swelled, and capillary basement membrane injury gradually increased. The above changes were most apparent at 12 hours after injury, after which they gradually attenuated. Aquaporin 4 expression positively correlated with brain water content and the blood-brain barrier index. Our experimental findings indicate that increasing aquaporin 4 expression and blood-brain barrier permeability after cerebral contusion and laceration injury in humans is involved in the formation of brain edema.展开更多
We established a stroke-prone renovascular hypertensive rat model by bilateral constriction of the renal artery with sliver loop clips. After ten weeks, middle cerebral artery occlusion was induced for 2 hours. The ra...We established a stroke-prone renovascular hypertensive rat model by bilateral constriction of the renal artery with sliver loop clips. After ten weeks, middle cerebral artery occlusion was induced for 2 hours. The rats then received electro-acupuncture at Baihui （DU 20） and Dazhui （DU 14） after onset of ischemia for 30 days. In situ hybridization study showed that electroacupuncture significantly reduced the number of neurocan mRNA-positive cells in the ischemic penumbra and hippocampal tissues of rats. Electron microscopy results demonstrated that the structure of neurons and blood vessels in the ischemic tissues were restored with electroacupuncture. Overall, these data suggest that electroacupuncture may protect neurons against ischemic reperfusion injury in stroke-prone renovascular hypertensive rats, which may be regulated by downregulation of expression of nerve inhibitory factor neurocan mRNA.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
In this study,the morphology and ultrastructure of the compound eye of L.lewisii were investigated using scanning electron microscopy(SEM),transmission electron microscopy(TEM),microcomputed tomography(μCT),and 3D re...In this study,the morphology and ultrastructure of the compound eye of L.lewisii were investigated using scanning electron microscopy(SEM),transmission electron microscopy(TEM),microcomputed tomography(μCT),and 3D reconstruction.The compound eye of L.lewisii was of the apposition type,with an average of 121.88±7.64 ommatidia in males and 119.00±4.71 ommatidia in females.Each ommatidium was composed of a biconvex cornea,an acone consisting of four cone cells,eight retinular cells along with the rhabdom,two primary pigment cells,and numerous secondary pigment cells.The open type of rhabdom in L.lewisii consists of six peripheral rhabdomeres contributed by the six peripheral retinular cells(R1~R6)and two vertically attached central rhabdomeres contributed by R7 and R8 respectively.The orientation of microvilli suggested a weak sensitivity to polarized light perception.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
Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic ...Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.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
Brain-computer interfaces(BCIs)represent an emerging technology that facilitates direct communication between the brain and external devices.In recent years,numerous review articles have explored various aspects of BC...Brain-computer interfaces(BCIs)represent an emerging technology that facilitates direct communication between the brain and external devices.In recent years,numerous review articles have explored various aspects of BCIs,including their fundamental principles,technical advancements,and applications in specific domains.However,these reviews often focus on signal processing,hardware development,or limited applications such as motor rehabilitation or communication.This paper aims to offer a comprehensive review of recent electroencephalogram(EEG)-based BCI applications in the medical field across 8 critical areas,encompassing rehabilitation,daily communication,epilepsy,cerebral resuscitation,sleep,neurodegenerative diseases,anesthesiology,and emotion recognition.Moreover,the current challenges and future trends of BCIs were also discussed,including personal privacy and ethical concerns,network security vulnerabilities,safety issues,and biocompatibility.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
Background:Magnetic resonance spectroscopy(MRS)represents a significant advancement in the noninvasive assessment of brain metabolism.MRS can provide valuable metabolic information and facilitate more accurate diagnos...Background:Magnetic resonance spectroscopy(MRS)represents a significant advancement in the noninvasive assessment of brain metabolism.MRS can provide valuable metabolic information and facilitate more accurate diagnoses of intrauterine fetal brain development than was previously possible.To obtain information regarding normal intrauterine fetal brain metabolism and to establish gestational age-specific reference values for normal fetal brain metabolites for subsequent use in MRS,we conducted MRS scans of normal fetal brains during mid-to late-term pregnancies,along with related processing.Methods:In this prospective study,MRS scans were conducted on 109 fetuses,with a total of 54 normal fetal brains enrolled on the basis of specific inclusion and exclusion criteria.We analyzed metabolic ratios,including the sum of N-acetylaspartate(NAA)and total N-acetylaspartate(tNAA),total choline(tCho),inositol(Ins),and total creatine(tCr),in relation to gestational age.Results:Gestational age was significantly correlated with specific metabolic ratios(Ins/tCr:r=-0.75,p<0.0001;tCho/tCr:r=-0.50,p<0.0001),especially tNAA/tCho(tNAA/tCho:r=0.54,p<0.0001)and tNAA/Ins(r=0.56,p<0.0001),providing a baseline for fetal brain metabolic assessment.Linear regression analysis was used to calculate regression lines for fetal brain metabolite ratios.Slopes were tested at p of 0.05.Conclusions:The current findings confirmed a significant correlation between fetal brain metabolites and gestational age,supporting the feasibility of establishing standard values for these metabolites in fetal brain assessment.展开更多
基金funded by the National Natural Science Foundation of China(No.32171770)Natural Science Foundation Program of Jilin Provincial Department of Education(No.JJKH20230074KJ).
文摘Rhododendron micranthum Turcz.is a shrub esteemed for its ornamental and medicinal attributes within the Changbai Mountain range of China.We selected 3-year saplings and subjected them to four distinct light condi-tions:full light(CK),70%light(L1),50%light(L2),and 30%light(L3)to investigate variations in morphology,photosynthetic responses,stomatal ultrastructure as well as the mechanisms through which these saplings adapt to differing lighting environments.The results indicate that L2 leaves exhibit significantly greater length,width,and petiole development compared to other treatments across varying intensities.Over time,chlorophyll content and PSII levels in L2-treated saplings surpass those observed in other treatments;Proline(PRO),malondialdehyde(MDA),and soluble protein(SP)contents are markedly lower under L2 treatment.Catalase(CAT)and superoxide dismutase(SOD)demonstrate significant correlations across various light con-ditions but respond differently among treatments,indicat-ing distinct species sensitivities to light intensity while both contribute to environmental stress resistance mechanisms.Findings reveal that R.micranthum saplings at 50%light intensity benefit from enhanced protection via antioxidant enzymes,and shading reduces osmotic adjustment sub-stances yet increases chlorophyll content.Stomatal length/width along with conductance rates and net photosynthesis rates for L2 exceed those of CK,suggesting an improved photosynthetic structure conducive to efficient photosynthe-sis under this condition.Thus,moderate shading represents optimal growth at 50%illumination,a critical factor promot-ing sapling development.This research elucidates the ideal environment for R.micranthum adaptation to varying light conditions supporting future conservation initiatives.
基金supported by the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2021A04013)the National Natural Science Foundation of China(82204610)+1 种基金the Qihang Talent Program(L2022046)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-041 and L2021029).
文摘Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewable,and clinical demand is increasingly difficult to meet,leading to a proliferation of counterfeit products.During prolonged geological burial,static pressure from the surrounding strata severely compromises the microstructural integrity of osteons in Os Draconis,but Os Draconis still largely retains the structural features of mammalian bone.Methods:Using verified authentic Os Draconis samples over 10,000 years old as a baseline,this study summarizes the ultrastructural characteristics of genuine Os Draconis.Employing electron probe microanalysis and optical polarized light microscopy,we examined 28 batches of authentic Os Draconis and 31 batches of counterfeits to identify their ultrastructural differences.Key points for ultrastructural identification of Os Draconis were compiled,and a new identification approach was proposed based on these differences.Results:Authentic Os Draconis exhibited distinct ultrastructural markers:irregularly shaped osteons with traversing fissures,deformed/displaced Haversian canals,and secondary mineral infill(predominantly calcium carbonate).Counterfeits showed regular osteon arrangements,absent traversal fissures,and homogeneous hydroxyapatite composition.Lab-simulated samples lacked structural degradation features.EPMA confirmed calcium carbonate infill in fossilized Haversian canals,while elemental profiles differentiated lacunae types(void vs.mineral-packed).Conclusion:The study established ultrastructural criteria for authentic Os Draconis identification:osteon deformation,geological fissures penetrating bone units,and heterogenous mineral deposition.These features,unattainable in counterfeits or modern processed bones,provide a cost-effective,accurate identification method.This approach bridges gaps in TCM material standardization and supports quality control for clinical applications.
基金funded by the Guangzhou Sci-ence and Technology Project(No.201803020017).
文摘The giant triton snail Charonia tritonis is a marine large carnivorous gastropoda inhabiting in the Indo-Pacific Ocean.Their splendid and highly organized Charonia tritonis shells are attractive;however few studies have been conducted on shell ultra-structure and pigmentation.The arrangements of crossed-lamellar structures were distinctive for the giant triton snail shell,showing three layers of mineral structures in the cross-section.The 1st-order and 2nd-order lamellae of the shell were around 10-20μm and the crystals in outer layers intersected at right angles in this species.They were identified as aragonite crystals by Raman scattering,and granular organic matrix were attached to the aragonite mineral phase closely.Furthermore,the dominant Raman spectra from polyene pigments in the shell were characterized at wavenumbers of 1123 cm^(-1)and 1504 cm^(-1),assigned to stretching vibrations of carbon-carbon single(C-C)and double(C=C)bonds,and the polyene chain was confirmed with 11-12 C-C bonds and 12-13 conju-gated C=C bonds.The research will lay a foundation for exploring the relationship between the calcareous shell and the formation of shell color in the giant triton snail.
文摘This study aimed to investigate aquaporin 4 expression and the ultrastructure of the blood-brain barrier at 2-72 hours following cerebral contusion injury, and correlate these changes to the formation of brain edema. Results revealed that at 2 hours after cerebral contusion and laceration injury, aquaporin 4 expression significantly increased, brain water content and blood-brain barrier permeability increased, and the number of pinocytotic vesicles in cerebral microvascular endothelia cells increased. In addition, the mitochondrial accumulation was observed. As contusion and laceration injury became aggravated, aquaporin 4 expression continued to increase, brain water content and blood-brain barrier permeability gradually increased, brain capillary endothelial cells and astrocytes swelled, and capillary basement membrane injury gradually increased. The above changes were most apparent at 12 hours after injury, after which they gradually attenuated. Aquaporin 4 expression positively correlated with brain water content and the blood-brain barrier index. Our experimental findings indicate that increasing aquaporin 4 expression and blood-brain barrier permeability after cerebral contusion and laceration injury in humans is involved in the formation of brain edema.
基金Research Projects of Science and Technology Bureau of Foshan City, No. 04080131the Administration Bureau of Traditional Chinese Medicine of Guangdong Province, No. 1050006the Natural Science Foundation of Guangdong Province, No. 8152800007000001
文摘We established a stroke-prone renovascular hypertensive rat model by bilateral constriction of the renal artery with sliver loop clips. After ten weeks, middle cerebral artery occlusion was induced for 2 hours. The rats then received electro-acupuncture at Baihui （DU 20） and Dazhui （DU 14） after onset of ischemia for 30 days. In situ hybridization study showed that electroacupuncture significantly reduced the number of neurocan mRNA-positive cells in the ischemic penumbra and hippocampal tissues of rats. Electron microscopy results demonstrated that the structure of neurons and blood vessels in the ischemic tissues were restored with electroacupuncture. Overall, these data suggest that electroacupuncture may protect neurons against ischemic reperfusion injury in stroke-prone renovascular hypertensive rats, which may be regulated by downregulation of expression of nerve inhibitory factor neurocan mRNA.
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.
文摘In this study,the morphology and ultrastructure of the compound eye of L.lewisii were investigated using scanning electron microscopy(SEM),transmission electron microscopy(TEM),microcomputed tomography(μCT),and 3D reconstruction.The compound eye of L.lewisii was of the apposition type,with an average of 121.88±7.64 ommatidia in males and 119.00±4.71 ommatidia in females.Each ommatidium was composed of a biconvex cornea,an acone consisting of four cone cells,eight retinular cells along with the rhabdom,two primary pigment cells,and numerous secondary pigment cells.The open type of rhabdom in L.lewisii consists of six peripheral rhabdomeres contributed by the six peripheral retinular cells(R1~R6)and two vertically attached central rhabdomeres contributed by R7 and R8 respectively.The orientation of microvilli suggested a weak sensitivity to polarized light perception.
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.82301486(to SL)and 82071325(to FY)Medjaden Academy&Research Foundation for Young Scientists,No.MJR202310040(to SL)+2 种基金Nanjing Medical University Science and Technique Development,No.NMUB20220060(to SL)Medical Scientific Research Project of Jiangsu Commission of Health,No.ZDA2020019(to JZ)Health China Buchang Zhiyuan Public Welfare Project for Heart and Brain Health,No.HIGHER202102(to QD).
文摘Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and disability.Accurate predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain undetermined.With innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental models.Differentially expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic stroke.Moreover,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.In particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic stroke.In this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and prognosis.Findings from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.
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(2021YFF1200602)the National Science Fund for Excellent Overseas Scholars(0401260011)+3 种基金the National Defense Science and Technology Innovation Fund of Chinese Academy of Sciences(c02022088)the Tianjin Science and Technology Program(20JCZDJC00810)the National Natural Science Foundation of China(82202798)the Shanghai Sailing Program(22YF1404200).
文摘Brain-computer interfaces(BCIs)represent an emerging technology that facilitates direct communication between the brain and external devices.In recent years,numerous review articles have explored various aspects of BCIs,including their fundamental principles,technical advancements,and applications in specific domains.However,these reviews often focus on signal processing,hardware development,or limited applications such as motor rehabilitation or communication.This paper aims to offer a comprehensive review of recent electroencephalogram(EEG)-based BCI applications in the medical field across 8 critical areas,encompassing rehabilitation,daily communication,epilepsy,cerebral resuscitation,sleep,neurodegenerative diseases,anesthesiology,and emotion recognition.Moreover,the current challenges and future trends of BCIs were also discussed,including personal privacy and ethical concerns,network security vulnerabilities,safety issues,and biocompatibility.
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.
基金supported by China Society for Maternal and Child Health Research(Gant/Award Number:2023CAMCHS003A17).
文摘Background:Magnetic resonance spectroscopy(MRS)represents a significant advancement in the noninvasive assessment of brain metabolism.MRS can provide valuable metabolic information and facilitate more accurate diagnoses of intrauterine fetal brain development than was previously possible.To obtain information regarding normal intrauterine fetal brain metabolism and to establish gestational age-specific reference values for normal fetal brain metabolites for subsequent use in MRS,we conducted MRS scans of normal fetal brains during mid-to late-term pregnancies,along with related processing.Methods:In this prospective study,MRS scans were conducted on 109 fetuses,with a total of 54 normal fetal brains enrolled on the basis of specific inclusion and exclusion criteria.We analyzed metabolic ratios,including the sum of N-acetylaspartate(NAA)and total N-acetylaspartate(tNAA),total choline(tCho),inositol(Ins),and total creatine(tCr),in relation to gestational age.Results:Gestational age was significantly correlated with specific metabolic ratios(Ins/tCr:r=-0.75,p<0.0001;tCho/tCr:r=-0.50,p<0.0001),especially tNAA/tCho(tNAA/tCho:r=0.54,p<0.0001)and tNAA/Ins(r=0.56,p<0.0001),providing a baseline for fetal brain metabolic assessment.Linear regression analysis was used to calculate regression lines for fetal brain metabolite ratios.Slopes were tested at p of 0.05.Conclusions:The current findings confirmed a significant correlation between fetal brain metabolites and gestational age,supporting the feasibility of establishing standard values for these metabolites in fetal brain assessment.
